Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates
Name
Amitriptyline
Accession Number
DB00321  (APRD00227)
Type
Small Molecule
Groups
Approved
Description

Amitriptyline hydrochloride, also known as Elavil, is a tricyclic antidepressant (TCA) with analgesic properties, widely used to treat depression and neuropathic pain 5. It was originally approved by the FDA in 1977 and manufactured by Sandoz 11.

Structure
Thumb
Synonyms
  • 10,11-dihydro-5-(γ-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene
  • 10,11-dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-Δ5,γ-propylamine
  • 3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine
  • 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine
  • 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene
  • 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene
  • 5-(γ-dimethylaminopropylidene)-5H-dibenzo[a,d][1,4]cycloheptadiene
  • Amitriptilina
  • Amitriptylin
  • Amitriptyline
  • Amitriptylinum
External IDs
MK 230 / N 750 / Ro 4-1575
Product Ingredients
IngredientUNIICASInChI Key
Amitriptyline hydrochloride26LUD4JO9K549-18-8KFYRPLNVJVHZGT-UHFFFAOYSA-N
Amitriptyline pamoateYX6VNM127F17086-03-2HBFZQWHVSYYTGA-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmitriptylineTabletOralSanis Health IncNot applicableNot applicableCanada
AmitriptylineTabletOralSanis Health IncNot applicableNot applicableCanada
AmitriptylineTabletOralSivem Pharmaceuticals Ulc2016-02-112018-11-01Canada
AmitriptylineTabletOralSivem Pharmaceuticals Ulc2016-02-112018-11-28Canada
AmitriptylineTabletOralSanis Health IncNot applicableNot applicableCanada
AmitriptylineTabletOralSivem Pharmaceuticals Ulc2016-02-112018-12-05Canada
Amitriptyline 10 TabTabletOralDuchesnay Inc.1981-12-312003-07-18Canada
Amitriptyline 25 TabTabletOralDuchesnay Inc.1981-12-312003-07-18Canada
Amitriptyline HCl Tab 25mgTabletOralD.C. Labs Limited1977-12-312003-07-11Canada
Amitriptyline HCl Tab 50mgTabletOralD.C. Labs Limited1977-12-312003-07-11Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ag-amitriptylineTabletOralAngita Pharma Inc.2018-12-24Not applicableCanada
Ag-amitriptylineTabletOralAngita Pharma Inc.2018-12-24Not applicableCanada
Ag-amitriptylineTabletOralAngita Pharma Inc.2018-12-24Not applicableCanada
Ag-amitriptylineTabletOralAngita Pharma Inc.Not applicableNot applicableCanada
Amitriptyline HydrochlorideTablet, film coated150 mg/1OralPhysicians Total Care, Inc.1995-07-25Not applicableUs
Amitriptyline HydrochlorideTablet, film coated25 mg/1OralMed Pharma Co., Ltd.2011-01-012013-10-18Us
Amitriptyline HydrochlorideTablet, film coated50 mg/1OralProficient Rx LP1997-09-11Not applicableUs
Amitriptyline HydrochlorideTablet, film coated25 mg/1OralA-S Medication Solutions1997-09-112013-06-28Us
Amitriptyline HydrochlorideTablet, film coated75 mg/1OralRemedy Repack2006-11-132016-02-17Us
Amitriptyline HydrochlorideTablet, film coated10 mg/1OralUnit Dose Services1977-11-21Not applicableUs50436 307120180907 15195 1hu7pju
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Apo Peram Tab 2-25Amitriptyline hydrochloride (25 mg) + Perphenazine (2 mg)TabletOralApotex Corporation1977-12-312011-08-05Canada
Apo Peram Tab 3-15Amitriptyline hydrochloride (15 mg) + Perphenazine (3 mg)TabletOralApotex Corporation1977-12-312011-08-05Canada
Chlordiazepoxide and Amitriptyline HClAmitriptyline hydrochloride (25 mg/1) + Chlordiazepoxide (10 mg/1)TabletOralPar Pharmaceutical1988-05-09Not applicableUs
Chlordiazepoxide and Amitriptyline HClAmitriptyline hydrochloride (12.5 mg/1) + Chlordiazepoxide (5 mg/1)TabletOralPar Pharmaceutical1988-05-09Not applicableUs
Chlordiazepoxide and Amitriptyline HydrochlorideAmitriptyline hydrochloride (27.98 mg/1) + Chlordiazepoxide (10 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.1986-12-10Not applicableUs00378 0277 01 nlmimage10 74133a79
Chlordiazepoxide and Amitriptyline HydrochlorideAmitriptyline hydrochloride (12.5 mg/1) + Chlordiazepoxide (5 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.1994-12-092010-09-30Us
Chlordiazepoxide and Amitriptyline HydrochlorideAmitriptyline hydrochloride (14 mg/1) + Chlordiazepoxide (5 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.1986-12-10Not applicableUs
Chlordiazepoxide and Amitriptyline HydrochlorideAmitriptyline hydrochloride (25 mg/1) + Chlordiazepoxide (10 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.1994-12-092010-09-30Us
Elavil Plus TabAmitriptyline hydrochloride (25 mg) + Perphenazine (2 mg)TabletOralTriton Pharma Inc1973-12-312003-03-08Canada
Etrafon 2 10Amitriptyline hydrochloride (10 mg) + Perphenazine (2 mg)TabletOralSchering Plough1970-12-312006-08-01Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Equipto - Amitriptyline External Cream Compounding KitAmitriptyline hydrochloride (1 g/2.4g)KitTopicalAlvix Laboratories2015-01-202018-03-08Us
Sentravil PM-25Amitriptyline hydrochloride (25 mg/1) + Choline (250 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUs
ZyvodolAmitriptyline hydrochloride (4 g/4g) + Diclofenac sodium (3 g/3g) + Lidocaine hydrochloride (2.5 g/2.5g) + Prilocaine hydrochloride (2.5 g/2.5g)KitTopicalAccumix Pharmaceuticals2014-12-152015-07-17Us
International/Other Brands
Adepril (Teofarma) / Amitryp (Raza) / Conmitrip (Condrugs) / Endep (Alphapharm) / Fiorda (Driburg) / Kamitrin (Saga) / Laroxyl (Deva) / Latilin (La Pharmaceuticals) / Maxitrip (Invision) / Redomex (Lundbeck) / Saroten (Lundbeck) / Sarotex (Lundbeck) / Sarotex Retard (Lundbeck) / Syneudon (Krewel Meuselbach) / Tryptanol (Merck Sharp & Dohme) / Tryptizol (Algorithm) / Uxen Retard (Sanofi-Aventis)
Categories
UNII
1806D8D52K
CAS number
50-48-6
Weight
Average: 277.4033
Monoisotopic: 277.183049741
Chemical Formula
C20H23N
InChI Key
KRMDCWKBEZIMAB-UHFFFAOYSA-N
InChI
InChI=1S/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
IUPAC Name
dimethyl(3-{tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine
SMILES
CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12

Pharmacology

Indication

This drug in indicated for the following conditions Label:

Major depressive disorder in adults

Management of neuropathic pain in adults

Prophylactic treatment of chronic tension-type headache (CTTH) in adults

Prophylactic treatment of migraine in adults

Treatment of nocturnal enuresis in children aged 6 years and above when organic pathology, including spina bifida and related disorders, have been excluded and no response has been achieved to all other non-drug and drug treatments, including antispasmodics and vasopressin-related products. This product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis Label

Off-label uses: irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation, fibromyalgia, and insomnia

Associated Conditions
Pharmacodynamics

Effects in pain and depression

Amitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative properties Label. Clinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed with post-herpetic neuralgia and 3/4 of patients diagnosed with diabetic neuropathic pain, and neurogenic pain syndromes that are frequently unresponsive to narcotic analgesics. Amitriptyline has also shown efficacy in diverse groups of patients with chronic non-malignant pain. There have also been some studies showing efficacy in managing fibromyalgia (an off-label use of this drug) 5, 8.

Cardiovascular and Anticholinergic Effects

Amitriptyline has strong anticholinergic properties and may cause ECG changes and quinidine-like effects on the heart 12. Amitriptyline may inhibit ion channels, which are necessary for cardiac repolarization (hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, amitriptyline may increase the risk for cardiac arrhythmia Label. Orthostatic hypotension and tachycardia can be a problem in elderly patients receiving this drug at normal doses for depression. There is evidence in the literature that these effects may occur, rarely, at the lower dosages utilized in the treatment of pain. As with any other tricyclic antidepressant agent, increased glucose levels can occur with amitriptyline 6.

Effects on seizure threshold

This drug also decreases the convulsive threshold and causes alterations in EEG and sleep patterns 12.

Mechanism of action

The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain Label, 10. These amines are important in regulating mood. The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects 9. This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms.

Whether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown 6.

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
inhibitor
Humans
ASodium-dependent serotonin transporter
inhibitor
Humans
A5-hydroxytryptamine receptor 2A
antagonist
Humans
U5-hydroxytryptamine receptor 1A
inhibitor
inducer
Humans
UDelta-type opioid receptor
agonist
Humans
UKappa-type opioid receptor
agonist
Humans
UHigh affinity nerve growth factor receptor
agonist
activator
Humans
UBDNF/NT-3 growth factors receptor
agonist
Humans
NAlpha-1A adrenergic receptor
antagonist
inhibitor
Humans
NAlpha-1D adrenergic receptor
antagonist
Humans
NAlpha-2A adrenergic receptor
antagonist
agonist
Humans
NHistamine H1 receptor
antagonist
Humans
NPotassium voltage-gated channel subfamily KQT member 2
inhibitor
Humans
NPotassium voltage-gated channel subfamily A member 1
inhibitor
Humans
UHistamine H2 receptor
blocker
Humans
UHistamine H4 receptor
binder
Humans
USigma non-opioid intracellular receptor 1
agonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
U5-hydroxytryptamine receptor 7
antagonist
Humans
U5-hydroxytryptamine receptor 1D
binder
Humans
UMu-type opioid receptor
binder
Humans
U5-hydroxytryptamine receptor 1B
binder
Humans
U5-hydroxytryptamine receptor 6
antagonist
Humans
UPotassium voltage-gated channel subfamily KQT member 3
inhibitor
Humans
U5-hydroxytryptamine receptor 1C
antagonist
Rat
UMuscarinic acetylcholine receptor
ligand
Humans
UHERG human cardiac K+ channel
blocker
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption

Rapidly absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations are reached 2-12 hours after oral or intramuscular administration Label. Steady-state plasma concentrations vary greatly and this variation may be due to genetic differences 12.

Volume of distribution

The apparent volume of distribution (Vd)β estimated after intravenous administration is 1221 L±280 L; range 769-1702 L (16±3 L/kg) Label. It is found widely distributed throughout the body 6. Amitriptyline and the main metabolite nortriptyline pass across the placental barrier and small amounts are present in breast milk Label.

Protein binding

Very highly protein bound (95%) in plasma and tissues Label.

Metabolism

In vitro, the metabolism of amitriptyline occurs mainly by demethylation (CYP2C19, CYP3A4) as well as hydroxylation (CYP2D6) followed by conjugation with glucuronic acid. Other isozymes involved in amitriptyline metabolism are CYP1A2 and CYP2C9. The metabolism of this drug is subject to genetic polymorphisms. The main active metabolite is the secondary amine, nortriptyline Label.

Nortriptyline is a stronger inhibitor of noradrenaline than of serotonin uptake, while amitriptyline inhibits the uptake of noradrenaline and serotonin with equal efficacy. Other metabolites such as cis- and trans-10-hydroxyamitriptyline and cis- and trans-10-hydroxynortriptyline have the same pharmacologic profile as nortriptyline but are significantly weaker. Demethylnortriptyline and amitriptyline N oxide are only present in plasma in negligible amounts; the latter is mostly inactive Label.

Route of elimination

Amitriptyline and its metabolites are mainly excreted in the urine. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with approximately 2% of unchanged drug appearing in the urine Label. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours Label. Small amounts are excreted in feces via biliary elimination 12.

Half life

The elimination half-life (t1⁄2 β) amitriptyline after peroral administration is about 25 hours (24.65 ± 6.31 hours; range 16.49-40.36 hours) Label.

Clearance

The mean systemic clearance (Cls) is 39.24 ± 10.18 L/h (range: 24.53-53.73 L/h) Label. No clear effect of older age on the pharmacokinetics of amitriptyline has been determined, although it is possible that clearance may be decreased 6.

Toxicity

Toxicity Data: Oral TDLO (child): 4167 μg/kg; Oral TDLO (man): 714 μg/kg/1D (intermittent); Oral TDLO (woman): 10 mg/kg 12.

Ingestion of 750 mg or more by an adult may result in severe toxicity. The effects in overdose are further increased by simultaneous ingestion of alcohol and another psychotropic agent Label. Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma, among others Label, 12.

Use in pregnancy

For amitriptyline, only limited clinical data are available regarding its use in pregnancy. Amitriptyline is not recommended during pregnancy unless clearly required and only after careful consideration of both risks and benefits Label.

Use in breastfeeding

Amitriptyline and its metabolites are excreted into breast milk (corresponding to 0.6 % - 1 % of the maternal dose). A risk to the suckling child must be considered. A decision should be made as to whether it is appropriate to discontinue breastfeeding or to discontinue/abstain from the therapy of this medicinal product, considering the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Effects on fertility

Animal studies have shown reproductive toxicity. No data on the effects of amitriptyline on human fertility are available Label.

Mutagenesis and carcinogenesis

The genotoxic potential of amitriptyline has been investigated in various in vitro and in vivo studies. Although these investigations showed some contradictory results, a potential of amitriptyline to lead to chromosome abnormalities cannot be excluded. Long-term carcinogenicity studies have not been performed to this date Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*4(A;A)A AlleleEffect Directly StudiedPatients with this genotype have reduced metabolism of amitriptyline.Details
Multidrug resistance protein 1---(C;C) / (C;T)C AlleleEffect Directly StudiedPatients with this genotype have an increased likelihood of remission when using amitriptyline to treat major depressive disorderDetails
Cytochrome P450 2C19CYP2C19*2(A;A) / (A;G)G > ADirectly Studied EffectPatients with this genotype have reduced metabolism of amitriptyline.Details
Multidrug resistance protein 1---(C;C) / (C;T)T > CEffect Directly StudiedPatients with this genotype have increased risk of adverse events with amitriptylineDetails
Cytochrome P450 2D6CYP2D6*3Not Available2549delAEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableA alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline.Details
Cytochrome P450 2C19CYP2C19*2Not Available681G>AEffect Directly StudiedThe presence of this polymorphism in CYP2C19 is associated with poor metabolism of amitriptyline.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AEffect Directly StudiedThe presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of amitriptyline.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*3Not Available636G>AADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*4Not Available1A>GADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*6Not Available395G>AADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all ADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GADR InferredThose with the AA or AG genotype are poor metabolizers of amitriptylineDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableG alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline.Details
Cytochrome P450 2D6CYP2D6*4Not Available3877G>AEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of amitriptyline.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Amitriptyline.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Amitriptyline.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Amitriptyline can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypertension can be increased when Amitriptyline is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Amitriptyline is combined with 1-benzylimidazole.
1,10-PhenanthrolineThe therapeutic efficacy of Amitriptyline can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedioneAmitriptyline may decrease the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Amitriptyline can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Amitriptyline can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of Amitriptyline can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Avoid St.John's Wort.
  • Take with food to reduce irritation.

References

Synthesis Reference

Manfred Durr, Benedikt Gajdos, Klaus-Dieter Gneuss, Ekkehard Harhausen, Jurgen Seidel, "Pharmaceutical amitriptylin oxide preparation and process for its manufacture." U.S. Patent US4567202, issued January 28, 1986.

US4567202
General References
  1. Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6. [PubMed:15943846]
  2. Hisaoka K, Tsuchioka M, Yano R, Maeda N, Kajitani N, Morioka N, Nakata Y, Takebayashi M: Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. J Biol Chem. 2011 Jun 17;286(24):21118-28. doi: 10.1074/jbc.M111.224683. Epub 2011 Apr 22. [PubMed:21515689]
  3. Yan L, Wang Q, Fu Q, Ye Q, Xiao H, Wan Q: Amitriptyline inhibits currents and decreases the mRNA expression of voltage-gated sodium channels in cultured rat cortical neurons. Brain Res. 2010 Jun 8;1336:1-9. doi: 10.1016/j.brainres.2010.04.016. Epub 2010 Apr 14. [PubMed:20398637]
  4. Olesen OV, Linnet K: Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology. 1997 Nov;55(5):235-43. doi: 10.1159/000139533. [PubMed:9399333]
  5. Lawson K: A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia. Biomedicines. 2017 May 17;5(2). pii: biomedicines5020024. doi: 10.3390/biomedicines5020024. [PubMed:28536367]
  6. Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [PubMed:8736630]
  7. Guaiana G, Barbui C, Hotopf M: Amitriptyline versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev. 2003;(2):CD004186. doi: 10.1002/14651858.CD004186 . [PubMed:12804503]
  8. Nishishinya B, Urrutia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G: Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008 Dec;47(12):1741-6. doi: 10.1093/rheumatology/ken317. Epub 2008 Aug 12. [PubMed:18697829]
  9. Moret C, Briley M: The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):9-13. doi: 10.2147/NDT.S19619. Epub 2011 May 31. [PubMed:21750623]
  10. Gupta SK, Shah JC, Hwang SS: Pharmacokinetic and pharmacodynamic characterization of OROS and immediate-release amitriptyline. Br J Clin Pharmacol. 1999 Jul;48(1):71-8. [PubMed:10383563]
  11. Amitriptyline FDA information, Approval [Link]
  12. Elavil Monograph [File]
  13. Safety data sheet, amitriptyline [File]
External Links
Human Metabolome Database
HMDB0014466
KEGG Drug
D07448
KEGG Compound
C06824
PubChem Compound
2160
PubChem Substance
46508798
ChemSpider
2075
BindingDB
50020712
ChEBI
2666
ChEMBL
CHEMBL629
Therapeutic Targets Database
DNC001466
PharmGKB
PA448385
Guide to Pharmacology
GtP Drug Page
HET
TP0
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amitriptyline
ATC Codes
N06AA09 — AmitriptylineN06CA01 — Amitriptyline and psycholeptics
AHFS Codes
  • 28:16.04.28 — Tricyclics and Other Norepinephrine-reuptake Inhibitors
PDB Entries
3apv / 5ha9
FDA label
Download (1 MB)
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceMembrane Transport / Metabolism, Drug1
1CompletedOtherDepressive Disorders1
1CompletedTreatmentHealthy Volunteers2
1Not Yet RecruitingNot AvailableDepression1
1, 2CompletedTreatmentFibromyalgia1
2CompletedTreatmentAdhesive Capsulitis1
2CompletedTreatmentBrain Injury / Post-Traumatic Headaches1
2CompletedTreatmentCarpal Tunnel Syndrome (CTS) / Cumulative Trauma Disorders / Pain / Repetitive Strain Injury1
2CompletedTreatmentChronic Oral Food Refusal1
2CompletedTreatmentCystic Fibrosis (CF) / Infection NOS / Pseudomonas Aeruginosa1
2CompletedTreatmentDiabetic Peripheral Neuropathy (DPN) / Neuralgia1
2CompletedTreatmentFibromyalgia / Human Growth Hormone Deficiency1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Peripheral Nervous System Diseases1
2CompletedTreatmentMajor Depressive Disorder (MDD)1
2RecruitingBasic ScienceHeadache / Migraine / Migraine Disorders1
2TerminatedTreatmentHypoglycemia Unawareness / Type1 Diabetes Mellitus1
2TerminatedTreatmentPruritus1
2Unknown StatusTreatmentCystic Fibrosis (CF) / Pneumonia1
2Unknown StatusTreatmentGallbladder Dyskinesia1
2Unknown StatusTreatmentIntervertebral Disc Displacement / Intervertebral Disc Herniation1
2, 3CompletedTreatmentDiabetes Mellitus (DM) / Peripheral neuropathy1
2, 3CompletedTreatmentDyspepsia and Other Specified Disorders of Function of Stomach1
2, 3CompletedTreatmentFemale Genital Diseases1
2, 3Enrolling by InvitationTreatmentChronic Laryngeal Neuropathy / Laryngeal Diseases1
2, 3TerminatedTreatmentChronic Laryngeal Neuropathy / Laryngeal Diseases1
2, 3Unknown StatusTreatmentFibromyalgia1
3Active Not RecruitingTreatmentPain1
3CompletedSupportive CareChronic Myeloproliferative Disorders / Leukemias / Lymphoproliferative Disorders / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Neurologic toxicity / Pain / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedSupportive CareNeurologic toxicity / Pain / Peripheral neuropathy / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentBladder Diseases / Interstitial Cystitis1
3CompletedTreatmentMajor Depressive Disorder (MDD)1
3CompletedTreatmentMigraine1
3CompletedTreatmentNeuropathic Pain Secondary to Radiation Therapy1
3CompletedTreatmentUnipolar Depression1
3RecruitingPreventionPostoperative pain1
3RecruitingTreatmentAmitriptyline / Hansen's Disease / Leprosy Neuropathy / Pain, Neuropathic1
3RecruitingTreatmentVulvodynia1
3TerminatedPreventionHeadache / Migraine / Migraine Disorders1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentInsomnia1
3Unknown StatusTreatmentHeadache1
3Unknown StatusTreatmentMalignancies / Neuralgia1
4CompletedTreatmentAnxiety Disorders / Moods Disorders / Schizophrenic Disorders1
4CompletedTreatmentFibromyalgia2
4CompletedTreatmentFunctional Gastrointestinal Disorders1
4CompletedTreatmentNeck Pain1
4CompletedTreatmentNeuropathic Pain Caused by Lumbar Radicular Pain1
4CompletedTreatmentPain, Chronic2
4CompletedTreatmentPain / Postoperative pain / Traumatic Amputations1
4CompletedTreatmentPain / Spinal Cord Injuries (SCI)1
4Enrolling by InvitationPreventionChronic Daily Headache / Transformed Migraine1
4RecruitingTreatmentMyofacial Pain1
4TerminatedTreatmentHeadache1
4TerminatedTreatmentNeuropathic Chronic Pain1
4Unknown StatusNot AvailableMajor Depressive Disorder (MDD)1
4WithdrawnTreatmentDiarrhoea Predominant Irritable Bowel Syndrome / Quality of Life1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedBasic ScienceHeadache, Tension-Type1
Not AvailableCompletedOtherMigraine / Preventive Treatment1
Not AvailableCompletedTreatmentChronic Pelvic Pain1
Not AvailableCompletedTreatmentFibromyalgia / Sleep Initiation and Maintenance Disorders1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Peripheral Nervous System Diseases1
Not AvailableCompletedTreatmentMigraine1
Not AvailableNot Yet RecruitingNot AvailableIrritable Bowel Syndrome (IBS)1
Not AvailableTerminatedTreatmentMajor Depressive Disorder (MDD)1
Not AvailableUnknown StatusTreatmentFunctional Dyspepsia1
Not AvailableUnknown StatusTreatmentTreatment Resistant Depression (TRD)1

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
  • Watson laboratories inc
  • Astrazeneca pharmaceuticals lp
  • Bristol myers squibb co
  • Warner chilcott div warner lambert co
  • American therapeutics inc
  • Caraco pharmaceutical laboratories ltd
  • Copley pharmaceutical inc
  • Halsey drug co inc
  • Lederle laboratories div american cyanamid co
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Pliva inc
  • Purepac pharmaceutical co
  • Roxane laboratories inc
  • Sandoz inc
  • Superpharm corp
  • Teva pharmaceuticals usa inc
  • Ucb inc
  • Usl pharma inc
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals inc
  • West ward pharmaceutical corp
Packagers
  • 4uOrtho LLC
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Blenheim Pharmacal
  • Bryant Ranch Prepack
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Caremark LLC
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Group Health Cooperative
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Legacy Pharmaceuticals Packaging LLC
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Nanjing Famu Chemicals Co. Ltd.
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Valeant Ltd.
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
TabletOral10 mg/1
TabletOral100 mg/1
TabletOral150 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral75 mg/1
TabletOral
TabletOral
SyrupOral
KitTopical1 g/2.4g
Tablet, film coatedOral
KitOral
KitTopical
Prices
Unit descriptionCostUnit
Amitriptyline hcl powder7.34USD g
Amitriptyline hcl 150 mg tablet1.18USD tablet
Amitriptyline hcl 100 mg tablet0.66USD tablet
Amitriptyline hcl 75 mg tablet0.54USD tablet
Apo-Amitriptyline 75 mg Tablet0.38USD tablet
Amitriptyline hcl 50 mg tablet0.37USD tablet
Amitriptyline hcl 10 mg tablet0.3USD tablet
Apo-Amitriptyline 50 mg Tablet0.25USD tablet
Amitriptyline hcl 25 mg tablet0.21USD tablet
Apo-Amitriptyline 25 mg Tablet0.13USD tablet
Apo-Amitriptyline 10 mg Tablet0.07USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)196-197https://www.chemicalbook.com/ChemicalProductProperty_US_CB1159271.aspx
boiling point (°C)410.26°C (rough estimate)https://www.chemicalbook.com/ChemicalProductProperty_US_CB1159271.aspx
water solubilityfreely soluble in waterhttps://pdf.hres.ca/dpd_pm/00043995.PDF
logP4.92https://pdfs.semanticscholar.org/6fc5/ceca026da3b93fb450ece63df320b5597ca2.pdf
logS-4.39https://www.acdlabs.com/download/publ/2007/low_quality_predictions.pdf
pKa9.4https://www.chemicalbook.com/ChemicalProductProperty_US_CB1159271.aspx
Predicted Properties
PropertyValueSource
Water Solubility0.0045 mg/mLALOGPS
logP5.1ALOGPS
logP4.81ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity101.51 m3·mol-1ChemAxon
Polarizability33.74 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9941
Blood Brain Barrier+0.9512
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.7567
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.6447
Renal organic cation transporterInhibitor0.7955
CYP450 2C9 substrateNon-substrate0.7826
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7501
CYP450 1A2 substrateInhibitor0.7324
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9158
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6955
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8127
BiodegradationNot ready biodegradable0.8727
Rat acute toxicity2.9697 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7531
hERG inhibition (predictor II)Inhibitor0.6767
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.48 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-9010000000-2afae55587735e5a8ce1
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9210000000-989cd234a8cdf04c5f69
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05po-5890000000-4cce07a2d07337e4ce90
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1590000000-35080e23f36a6ed30005
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-66d4e2dc0e65719c8949
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0190000000-18fad36e219aa0091dcf
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05o3-3980000000-bd3bb65e31837e45268f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0aou-2940000000-c3c71a4ddeb15eb427b4
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05mo-2930000000-f6bc4a5899aed7b3047e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0fr6-2930000000-c348567e54820b6ddff3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-fae7f4e9cc1f20e9a2dd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0190000000-42ecf4fcfbd4bd102322
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05o3-3980000000-69e1e5d2fdd46de25ba4
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0aou-2940000000-853a0f18213b600d48ae
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05mo-2930000000-9493535ee63a9a708527
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0fr6-2930000000-fba97ca65c4bf1940385
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1690000000-99ea606fc86c8400c4ce
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0090000000-8155764b5e04e44b4ca2
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0190000000-7e3a5d063f540759d63f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0apl-0960000000-e35715828f4c02816f19
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0lfu-0940000000-a6befd2c2f6b01d0c348
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0v03-0940000000-cab5377d28cf5d892f47
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-2590000000-85fb81c2565771c07a12

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Dibenzocycloheptenes
Sub Class
Not Available
Direct Parent
Dibenzocycloheptenes
Alternative Parents
Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Dibenzocycloheptene / Tertiary aliphatic amine / Tertiary amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine / Aromatic homopolycyclic compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tertiary amine, organic tricyclic compound (CHEBI:2666)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [PubMed:14744476]
  2. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
  3. Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [PubMed:8736630]
  4. Elavil Monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [PubMed:16140280]
  2. Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29. [PubMed:16032412]
  3. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [PubMed:14744476]
  4. Ushijima K, Sakaguchi H, Sato Y, To H, Koyanagi S, Higuchi S, Ohdo S: Chronopharmacological study of antidepressants in forced swimming test of mice. J Pharmacol Exp Ther. 2005 Nov;315(2):764-70. Epub 2005 Aug 3. [PubMed:16079297]
  5. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
  6. Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [PubMed:17689532]
  7. Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [PubMed:8736630]
  8. Elavil Monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Pandey DK, Mahesh R, Kumar AA, Rao VS, Arjun M, Rajkumar R: A novel 5-HT(2A) receptor antagonist exhibits antidepressant-like effects in a battery of rodent behavioural assays: approaching early-onset antidepressants. Pharmacol Biochem Behav. 2010 Jan;94(3):363-73. doi: 10.1016/j.pbb.2009.09.018. Epub 2009 Oct 2. [PubMed:19800913]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Some studies suggest this receptor is upregulated by amitriptyline and some suggest it is down regulated by amitriptyline.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Rossi DV, Valdez M, Gould GG, Hensler JG: Chronic administration of venlafaxine fails to attenuate 5-HT1A receptor function at the level of receptor-G protein interaction. Int J Neuropsychopharmacol. 2006 Aug;9(4):393-406. doi: 10.1017/S1461145705005754. Epub 2005 Jul 22. [PubMed:16035959]
  3. Lesch KP, Disselkamp-Tietze J, Schmidtke A: 5-HT1A receptor function in depression: effect of chronic amitriptyline treatment. J Neural Transm Gen Sect. 1990;80(2):157-61. [PubMed:2317317]
  4. Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE: Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9;231(2):223-9. [PubMed:8453978]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
References
  1. Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. doi: 10.1124/jpet.109.159939. Epub 2009 Oct 14. [PubMed:19828880]
  2. Benbouzid M, Gaveriaux-Ruff C, Yalcin I, Waltisperger E, Tessier LH, Muller A, Kieffer BL, Freund-Mercier MJ, Barrot M: Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia. Biol Psychiatry. 2008 Mar 15;63(6):633-6. doi: 10.1016/j.biopsych.2007.06.016. Epub 2007 Aug 13. [PubMed:17693391]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. doi: 10.1124/jpet.109.159939. Epub 2009 Oct 14. [PubMed:19828880]
  2. Carydakis C, Bourhim N, Giraud P, Cantau P, Oliver C, Castanas E: [Direct interaction of tricyclic antidepressants with opiate binding sites in the bovine adrenal medulla]. C R Acad Sci III. 1986;302(11):419-22. [PubMed:3013380]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Activator
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...
Gene Name
NTRK1
Uniprot ID
P04629
Uniprot Name
High affinity nerve growth factor receptor
Molecular Weight
87496.465 Da
References
  1. Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. doi: 10.1016/j.chembiol.2009.05.010. [PubMed:19549602]
  2. Zheng X, Chen F, Zheng T, Huang F, Chen J, Tu W: Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons. Medicine (Baltimore). 2016 May;95(18):e3559. doi: 10.1097/MD.0000000000003559. [PubMed:27149473]
  3. Rantamaki T, Vesa L, Antila H, Di Lieto A, Tammela P, Schmitt A, Lesch KP, Rios M, Castren E: Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade. PLoS One. 2011;6(6):e20567. doi: 10.1371/journal.pone.0020567. Epub 2011 Jun 7. [PubMed:21666748]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differenti...
Gene Name
NTRK2
Uniprot ID
Q16620
Uniprot Name
BDNF/NT-3 growth factors receptor
Molecular Weight
91998.175 Da
References
  1. Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. doi: 10.1016/j.chembiol.2009.05.010. [PubMed:19549602]
  2. Cai J, Hua F, Yuan L, Tang W, Lu J, Yu S, Wang X, Hu Y: Potential therapeutic effects of neurotrophins for acute and chronic neurological diseases. Biomed Res Int. 2014;2014:601084. doi: 10.1155/2014/601084. Epub 2014 Apr 9. [PubMed:24818146]
  3. O'Neill E, Kwok B, Day JS, Connor TJ, Harkin A: Amitriptyline protects against TNF-alpha-induced atrophy and reduction in synaptic markers via a Trk-dependent mechanism. Pharmacol Res Perspect. 2016 Mar 8;4(2):e00195. doi: 10.1002/prp2.195. eCollection 2016 Apr. [PubMed:27069625]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Inhibitor
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [PubMed:20363235]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Curator comments
This information is based on the results of in vitro studies. Data in the literature regarding this target are limited.
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [PubMed:20363235]
  2. RBCB PDB resource [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. [PubMed:14757140]
  2. Charney DS, Heninger GR, Sternberg DE: Alpha-2 adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy. The effect of long-term amitriptyline treatment. Br J Psychiatry. 1983 Mar;142:265-75. [PubMed:6305451]
  3. Gray AM, Pache DM, Sewell RD: Do alpha2-adrenoceptors play an integral role in the antinociceptive mechanism of action of antidepressant compounds? Eur J Pharmacol. 1999 Aug 6;378(2):161-8. [PubMed:10478628]
  4. Cottingham C, Percival S, Birky T, Wang Q: Tricyclic antidepressants exhibit variable pharmacological profiles at the alpha(2A) adrenergic receptor. Biochem Biophys Res Commun. 2014 Aug 29;451(3):461-6. doi: 10.1016/j.bbrc.2014.08.024. Epub 2014 Aug 12. [PubMed:25128275]
Details
12. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Richelson E: Tricyclic antidepressants and histamine H1 receptors. Mayo Clin Proc. 1979 Oct;54(10):669-74. [PubMed:39202]
  3. Kachur JF, Allbee WE, Gaginella TS: Antihistaminic and antimuscarinic effects of amitriptyline on guinea pig ileal electrolyte transport and muscle contractility in vitro. J Pharmacol Exp Ther. 1988 May;245(2):455-9. [PubMed:2896792]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Data limited to in vitro study results.
General Function
Voltage-gated potassium channel activity
Specific Function
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current...
Gene Name
KCNQ2
Uniprot ID
O43526
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 2
Molecular Weight
95846.575 Da
References
  1. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:1990381...
Gene Name
KCNA1
Uniprot ID
Q09470
Uniprot Name
Potassium voltage-gated channel subfamily A member 1
Molecular Weight
56465.01 Da
References
  1. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683]
  2. Freysoldt A, Fleckenstein J, Lang PM, Irnich D, Grafe P, Carr RW: Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve. Br J Pharmacol. 2009 Oct;158(3):797-805. doi: 10.1111/j.1476-5381.2009.00347.x. Epub 2009 Aug 19. [PubMed:19694730]
Details
15. Histamine H2 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Blocker
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Angus JA, Black JW: Pharmacological assay of cardiac H2-receptor blockade by amitriptyline and lysergic acid diethylamide. Circ Res. 1980 Jun;46(6 Pt 2):I64-9. [PubMed:6103762]
  2. Traiffort E, Pollard H, Moreau J, Ruat M, Schwartz JC, Martinez-Mir MI, Palacios JM: Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I]iodoaminopotentidine. J Neurochem. 1992 Jul;59(1):290-9. [PubMed:1351926]
Details
16. Histamine H4 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Histamine receptor activity
Specific Function
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agoni...
Gene Name
HRH4
Uniprot ID
Q9H3N8
Uniprot Name
Histamine H4 receptor
Molecular Weight
44495.375 Da
References
  1. Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF: Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33. [PubMed:11179435]
  2. Connelly WM, Shenton FC, Lethbridge N, Leurs R, Waldvogel HJ, Faull RL, Lees G, Chazot PL: The histamine H4 receptor is functionally expressed on neurons in the mammalian CNS. Br J Pharmacol. 2009 May;157(1):55-63. doi: 10.1111/j.1476-5381.2009.00227.x. [PubMed:19413571]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma m...
Gene Name
SIGMAR1
Uniprot ID
Q99720
Uniprot Name
Sigma non-opioid intracellular receptor 1
Molecular Weight
25127.52 Da
References
  1. Villard V, Meunier J, Chevallier N, Maurice T: Pharmacological interaction with the sigma1 (sigma1)-receptor in the acute behavioral effects of antidepressants. J Pharmacol Sci. 2011;115(3):279-92. [PubMed:21427517]
  2. Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [PubMed:17689532]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Di Matteo V, De Blasi A, Di Giulio C, Esposito E: Role of 5-HT(2C) receptors in the control of central dopamine function. Trends Pharmacol Sci. 2001 May;22(5):229-32. [PubMed:11339973]
  2. Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J: Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996 Aug;126(3):234-40. [PubMed:8876023]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
This action is based on data from in vitro studies. Data in the literature are limited regarding this target action.
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [PubMed:20363235]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M: The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9. [PubMed:10997731]
  2. Liu J, Reid AR, Sawynok J: Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline. Eur J Pharmacol. 2013 Jan 5;698(1-3):213-9. doi: 10.1016/j.ejphar.2012.10.042. Epub 2012 Nov 6. [PubMed:23142373]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
Data in the literature regarding this target are limited. These data are based on the results of in vitro studies.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [PubMed:17689532]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
Data regarding this target action are limited in the literature.
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Hamon M, Gozlan H, Bourgoin S, Benoliel JJ, Mauborgne A, Taquet H, Cesselin F, Mico JA: Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline. Neuropharmacology. 1987 Jun;26(6):531-9. [PubMed:3037421]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
Data are based on in vitro studies. There is limited information about this target action in the literature.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Werling LL, Keller A, Frank JG, Nuwayhid SJ: A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Exp Neurol. 2007 Oct;207(2):248-57. Epub 2007 Jun 30. [PubMed:17689532]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Data based on in vitro studies. The information regarding this target in the literature is limited.
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. Sebben M, Ansanay H, Bockaert J, Dumuis A: 5-HT6 receptors positively coupled to adenylyl cyclase in striatal neurones in culture. Neuroreport. 1994 Dec 20;5(18):2553-7. [PubMed:7696602]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native ...
Gene Name
KCNQ3
Uniprot ID
O43525
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 3
Molecular Weight
96741.515 Da
References
  1. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683]
  2. Syeda R, Santos JS, Montal M: The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine. J Biol Chem. 2016 Feb 5;291(6):2931-7. doi: 10.1074/jbc.M115.683185. Epub 2015 Dec 1. [PubMed:26627826]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
Htr2c
Uniprot ID
P08909
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51916.005 Da
References
  1. Pithadia AB, Jain SM: 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials. J Clin Med Res. 2009 Jun;1(2):72-80. doi: 10.4021/jocmr2009.05.1237. Epub 2009 Jun 21. [PubMed:22505971]
  2. Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE: Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9;231(2):223-9. [PubMed:8453978]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Components:
References
  1. Goldman P, Scranton T, Messer WS Jr: Interaction of amitriptyline with muscarinic receptor subtypes in the rat brain. Neurochem Int. 1989;14(4):447-54. [PubMed:20504448]
  2. Dilsaver SC, Snider RM, Alessi NE: Amitriptyline supersensitizes a central cholinergic mechanism. Biol Psychiatry. 1987 Apr;22(4):495-507. [PubMed:3567263]
  3. Snyder SH, Yamamura HI: Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry. 1977 Feb;34(2):236-9. [PubMed:14603]
  4. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Blocker
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...

Components:
References
  1. Jo SH, Youm JB, Lee CO, Earm YE, Ho WK: Blockade of the HERG human cardiac K(+) channel by the antidepressant drug amitriptyline. Br J Pharmacol. 2000 Apr;129(7):1474-80. doi: 10.1038/sj.bjp.0703222. [PubMed:10742304]
  2. Teschemacher AG, Seward EP, Hancox JC, Witchel HJ: Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. Br J Pharmacol. 1999 Sep;128(2):479-85. [PubMed:10510461]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. [PubMed:8968657]
  2. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  3. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [PubMed:9131945]
  4. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [PubMed:11259560]
  5. Flockhart Table of Drug Interactions [Link]
  6. Amitriptyline FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  2. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [PubMed:11259560]
  3. Arici M, Ozhan G: The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population. Saudi Pharm J. 2017 Feb;25(2):294-297. doi: 10.1016/j.jsps.2016.06.001. Epub 2016 Jun 16. [PubMed:28344482]
  4. Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E: Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009 Sep;11(3):481-94. doi: 10.1208/s12248-009-9127-y. Epub 2009 Jul 10. [PubMed:19590965]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, Lee SS, Oh SW, Kim SW, Flockhart DA: Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos. 2002 Oct;30(10):1102-7. [PubMed:12228186]
  2. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [PubMed:11259560]
  3. Ryu S, Park S, Lee JH, Kim YR, Na HS, Lim HS, Choi HY, Hwang IY, Lee JG, Park ZW, Oh WY, Kim JM, Choi SE: A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans. Clin Transl Sci. 2017 Mar;10(2):93-101. doi: 10.1111/cts.12451. Epub 2017 Mar 14. [PubMed:28296334]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [PubMed:9131945]
  2. Attia TZ, Yamashita T, Hammad MA, Hayasaki A, Sato T, Miyamoto M, Yasuhara Y, Nakamura T, Kagawa Y, Tsujino H, Omar MA, Abdelmageed OH, Derayea SM, Uno T: Effect of cytochrome P450 2C19 and 2C9 amino acid residues 72 and 241 on metabolism of tricyclic antidepressant drugs. Chem Pharm Bull (Tokyo). 2014;62(2):176-81. [PubMed:24492587]
  3. Olesen OV, Linnet K: Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology. 1997 Nov;55(5):235-43. doi: 10.1159/000139533. [PubMed:9399333]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  2. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [PubMed:9131945]
  3. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [PubMed:11259560]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data based on in vitro studies. There are limited data in the literature regarding this enzyme action.
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [PubMed:11259560]
  2. Ekins S, Iyer M, Krasowski MD, Kharasch ED: Molecular characterization of CYP2B6 substrates. Curr Drug Metab. 2008 Jun;9(5):363-73. [PubMed:18537573]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. [PubMed:11259560]
  2. Martinez C, Garcia-Martin E, Blanco G, Gamito FJ, Ladero JM, Agundez JA: The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. Br J Clin Pharmacol. 2005 Jan;59(1):62-9. doi: 10.1111/j.1365-2125.2004.02183.x. [PubMed:15606441]
  3. Naraharisetti SB, Lin YS, Rieder MJ, Marciante KD, Psaty BM, Thummel KE, Totah RA: Human liver expression of CYP2C8: gender, age, and genotype effects. Drug Metab Dispos. 2010 Jun;38(6):889-93. doi: 10.1124/dmd.109.031542. Epub 2010 Feb 26. [PubMed:20190184]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Specific Function
Glucuronosyltransferase activity
Gene Name
UGT2B10
Uniprot ID
P36537
Uniprot Name
UDP-glucuronosyltransferase 2B10
Molecular Weight
60773.485 Da
References
  1. Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, Nakajima M: Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97. doi: 10.1124/dmd.113.051565. Epub 2013 Apr 23. [PubMed:23611809]
  2. Zhou D, Guo J, Linnenbach AJ, Booth-Genthe CL, Grimm SW: Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70. doi: 10.1124/dmd.109.030981. Epub 2010 Feb 4. [PubMed:20133892]
  3. Pattanawongsa A, Nair PC, Rowland A, Miners JO: Human UDP-Glucuronosyltransferase (UGT) 2B10: Validation of Cotinine as a Selective Probe Substrate, Inhibition by UGT Enzyme-Selective Inhibitors and Antidepressant and Antipsychotic Drugs, and Structural Determinants of Enzyme Inhibition. Drug Metab Dispos. 2016 Mar;44(3):378-88. doi: 10.1124/dmd.115.068213. Epub 2015 Dec 15. [PubMed:26669329]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, Nakajima M: Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97. doi: 10.1124/dmd.113.051565. Epub 2013 Apr 23. [PubMed:23611809]
  2. Zhou D, Guo J, Linnenbach AJ, Booth-Genthe CL, Grimm SW: Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70. doi: 10.1124/dmd.109.030981. Epub 2010 Feb 4. [PubMed:20133892]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. [PubMed:6108517]
  2. Banerjee T, Singh SK, Kishore N: Binding of naproxen and amitriptyline to bovine serum albumin: biophysical aspects. J Phys Chem B. 2006 Nov 30;110(47):24147-56. [PubMed:17125386]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. [PubMed:6108517]
  2. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [PubMed:2870173]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
There are conflicting data in the literature regarding amitriptyline as a substrate for p-glycoprotein.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Grauer MT, Uhr M: P-glycoprotein reduces the ability of amitriptyline metabolites to cross the blood brain barrier in mice after a 10-day administration of amitriptyline. J Psychopharmacol. 2004 Mar;18(1):66-74. doi: 10.1177/0269881104042831. [PubMed:15107187]
  2. O'Brien FE, Clarke G, Dinan TG, Cryan JF, Griffin BT: Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability. Int J Neuropsychopharmacol. 2013 Nov;16(10):2259-72. doi: 10.1017/S1461145713000692. Epub 2013 Aug 9. [PubMed:23931269]
  3. Abaut AY, Chevanne F, Le Corre P: Oral bioavailability and intestinal secretion of amitriptyline: Role of P-glycoprotein? Int J Pharm. 2007 Feb 7;330(1-2):121-8. doi: 10.1016/j.ijpharm.2006.09.026. Epub 2006 Sep 23. [PubMed:17092666]
  4. Uhr M, Steckler T, Yassouridis A, Holsboer F: Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology. 2000 Apr;22(4):380-7. doi: 10.1016/S0893-133X(99)00095-0. [PubMed:10700657]

Drug created on June 13, 2005 07:24 / Updated on November 22, 2019 04:03