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Identification
NameAmitriptyline
Accession NumberDB00321  (APRD00227)
TypeSmall Molecule
GroupsApproved
Description

Amitriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amitriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, amitriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amitriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).

Structure
Thumb
Synonyms
SynonymLanguageCode
10,11-dihydro-5-(gamma-Dimethylaminopropylidene)-5H-dibenzo(a,D)cyclohepteneNot AvailableNot Available
10,11-dihydro-N,N-Dimethyl-5H-dibenzo(a,D)heptalene-delta(5),gamma-propylamineNot AvailableNot Available
3-(10,11-dihydro-5H-Dibenzo(a,D)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamineNot AvailableNot Available
3-(10,11-dihydro-5H-Dibenzo[a,D]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amineNot AvailableNot Available
5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,D)cycloheptatrieneNot AvailableNot Available
5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,D)cyclohepteneNot AvailableNot Available
5-(gamma-Dimethylaminopropylidene)-5H-dibenzo[a,D][1,4]cycloheptadieneNot AvailableNot Available
AmitriptilinaNot AvailableDCIT
AmitriptylinGermanINN
AmitriptylineNot AvailableDCF, BAN
AmitriptylinumLatinINN
Salts
Name/CAS Structure Properties
Amitriptyline Hydrochloride
Thumb
  • InChI Key: KFYRPLNVJVHZGT-UHFFFAOYSA-N
  • Monoisotopic Mass: 313.15972748
  • Average Mass: 313.864
DBSALT000009
Brand names
NameCompany
AdeprilTeofarma
AmitrypRaza
ConmitripCondrugs
ElavilGerda
EndepAlphapharm
FiordaDriburg
KamitrinSaga
LaroxylDeva
LatilinLa Pharmaceuticals
MaxitripInvision
RedomexLundbeck
SarotenLundbeck
SarotexLundbeck
Sarotex RetardLundbeck
SyneudonKrewel Meuselbach
TryptanolMerck Sharp & Dohme
TryptanolSquare
TryptizolAlgorithm
Uxen RetardSanofi-Aventis
Brand mixtures
Brand NameIngredients
Elavil PlusAmitriptyline Hydrochloride + Perphenazine
EtrafonAmitriptyline Hydrochloride + Perphenazine
PMS-LevazineAmitriptyline Hydrochloride + Perphenazine
ProavilAmitriptyline Hydrochloride + Perphenazine
TriavilAmitriptyline Hydrochloride + Perphenazine
Categories
CAS number50-48-6
WeightAverage: 277.4033
Monoisotopic: 277.183049741
Chemical FormulaC20H23N
InChI KeyKRMDCWKBEZIMAB-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-[(2Z)-tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene]propyl})amine
SMILES
CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
Mass Specshow(7.48 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassDibenzocycloheptenes
SubclassNot Available
Direct parentDibenzocycloheptenes
Alternative parentsBenzene and Substituted Derivatives; Tertiary Amines; Polyamines
Substituentsbenzene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene connected by a cycloheptene ring.
Pharmacology
IndicationFor the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
PharmacodynamicsAmitriptyline, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is extremely sedating, and thus improvement of sleep patterns can be the first benefit of treatment. Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold. As with other antidepressants, several weeks of therapy may be required in order to realize the full clinical benefit of amitriptyline. Although not a labelled indication, amitriptyline is widely used in the management of chronic nonmalignant pain (e.g., post-herpetic neuralgia, fibromyalgia).
Mechanism of actionAmitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
AbsorptionRapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations occur 2-12 hours following oral or intramuscular administration.
Volume of distributionNot Available
Protein bindingVery highly protein bound (90% or more) in plasma and tissues
Metabolism

Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline.

SubstrateEnzymesProduct
Amitriptyline
NortriptylineDetails
Amitriptyline
E-10-HydroxyamitriptylineDetails
E-10-Hydroxyamitriptyline
E-10-HydroxynortriptylineDetails
E-10-Hydroxynortriptyline
Not Available
E-10-HydroxydesmethylnortriptylineDetails
Nortriptyline
E-10-HydroxynortriptylineDetails
Nortriptyline
Not Available
DesmethylnortriptylineDetails
Desmethylnortriptyline
E-10-HydroxydesmethylnortriptylineDetails
Route of eliminationVirtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination.
Half life10 to 50 hours, with an average of 15 hours
ClearanceNot Available
ToxicityLD50=350 mg/kg (in mice). 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. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs3892097 CYP2D6*4A AllelePoor drug metabolizer, lower dose requirements, higher risk for adverse side effects18070221
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs2032583 Not AvailableC AlleleImproved response to antidepressant medication17913323
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs2032583 Not AvailableA > GIncrease risk of adverse effects22641028
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs1045642 Not AvailableT Allele, homozygousPostural hypotension12082591
Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261
rs4244285 CYP2C19*2G > AThose with the AA or AG genotype are poor metabolizers of amitriptyline20531370
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs3892097 CYP2D6*4C > TIncrease risk of side effects and decrease drug metabolism18070221
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs3892097 CYP2D6*4C > TIncrease risk of side effects and decrease drug metabolism9918137
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9941
Blood Brain Barrier + 0.9512
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.7567
P-glycoprotein inhibitor I Inhibitor 0.8563
P-glycoprotein inhibitor II Inhibitor 0.6447
Renal organic cation transporter Inhibitor 0.7955
CYP450 2C9 substrate Non-substrate 0.7826
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.7501
CYP450 1A2 substrate Inhibitor 0.7324
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8933
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9158
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6955
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.8127
Biodegradation Not ready biodegradable 0.8727
Rat acute toxicity 2.9697 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7531
hERG inhibition (predictor II) Inhibitor 0.6767
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
Dosage forms
FormRouteStrength
Tablet, film coatedOral10 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral150 mg
Tablet, film coatedOral25 mg
Tablet, film coatedOral50 mg
Tablet, film coatedOral75 mg
Prices
Unit descriptionCostUnit
Amitriptyline hcl powder7.34USDg
Amitriptyline hcl 150 mg tablet1.18USDtablet
Amitriptyline hcl 100 mg tablet0.66USDtablet
Amitriptyline hcl 75 mg tablet0.54USDtablet
Apo-Amitriptyline 75 mg Tablet0.38USDtablet
Amitriptyline hcl 50 mg tablet0.37USDtablet
Amitriptyline hcl 10 mg tablet0.3USDtablet
Apo-Amitriptyline 50 mg Tablet0.25USDtablet
Amitriptyline hcl 25 mg tablet0.21USDtablet
Apo-Amitriptyline 25 mg Tablet0.13USDtablet
Apo-Amitriptyline 10 mg Tablet0.07USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point187-189.5Tristram, E.W. and Tull, R.J.; US. Patent 3,205,264: September 7,1965; assigned to Merck & Co., Inc.
water solubility9.71 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.92HANSCH,C ET AL. (1995)
logS-4.46ADME Research, USCD
pKa9.4SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0045ALOGPS
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
Spectra
Spectra
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 Reference
  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
External Links
ResourceLink
KEGG CompoundC06824
PubChem Compound2160
PubChem Substance46508798
ChemSpider2075
ChEBI2666
ChEMBLCHEMBL629
Therapeutic Targets DatabaseDNC001466
PharmGKBPA448385
IUPHAR200
Guide to Pharmacology200
Drug Product Database654515
RxListhttp://www.rxlist.com/cgi/generic/amitrip.htm
Drugs.comhttp://www.drugs.com/amitriptyline.html
WikipediaAmitriptyline
ATC CodesN06AA09
AHFS Codes
  • 28:16.04.28
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.6 KB)
Interactions
Drug Interactions
Drug
AltretamineRisk of severe hypotension
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AtazanavirAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if atazanavir if initiated, discontinued or dose changed.
ButabarbitalBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
ButalbitalBarbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
CarbamazepineCarbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.
CimetidineCimetidine may increase the effect of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if cimetidine is initiated, discontinued or dose changed.
CisaprideIncreased risk of cardiotoxicity and arrhythmias
ClonidineThe tricyclic antidepressant, amitriptyline, decreases the effect of clonidine.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroquinidine barbiturateDihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, amitriptyline.
DobutamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dobutamine.
DonepezilPossible antagonism of action
DopamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dopamine.
DuloxetinePossible increase in the levels of this agent when used with duloxetine
EphedraThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedra.
EphedrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedrine.
EpinephrineThe tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine.
FenoterolThe tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of fenoterol.
FluconazoleFluconazole may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
FluoxetineThe SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluoxetine is initiated, discontinued or dose changed.
FluvoxamineThe SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluvoxamine is initiated, discontinued or dose changed.
GalantaminePossible antagonism of action
GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
GuanethidineThe tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine.
IndacaterolConcomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
IobenguaneMay diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
IsocarboxazidPossibility of severe adverse effects
IsoprenalineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of isoproterenol.
KetoconazoleKetoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of amitriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ketoconazole is initiated, discontinued or dose changed.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MephentermineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of mephentermine.
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MetaraminolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of metaraminol.
MethoxamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine.
MoclobemidePossible severe adverse reaction with this combination
NorepinephrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine.
OrciprenalineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.
PhenelzinePossibility of severe adverse effects
PhenylephrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylephrine.
PhenylpropanolamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylpropanolamine.
PirbuterolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pirbuterol.
ProcaterolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of procaterol.
PseudoephedrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pseudoephedrine.
QuinidineAdditive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Quinidine barbiturateQuinidine barbiturate increases the effect of tricyclic antidepressant, amitriptyline.
RasagilinePossibility of severe adverse effects
RifabutinThe rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifabutin is initiated, discontinued or dose changed.
RifampicinThe rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifampin is initiated, discontinued or dose changed.
RitonavirRitonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
RivastigminePossible antagonism of action
SalbutamolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol.
SibutramineIncreased risk of CNS adverse effects
SparfloxacinIncreased risk of cardiotoxicity and arrhythmias
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amitriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TerbinafineTerbinafine may reduce the metabolism and clearance of Amitryptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Terbinafine is initiated, discontinued or dose changed.
TerbutalineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of terbutaline.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TramadolTramadol increases the risk of serotonin syndrome and seizures.
TranylcypromineIncreased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrimethobenzamideTrimethobenzamide and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TriprolidineTriprolidine and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VilazodoneMonitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZolmitriptanUse of two serotonin modulators, such as zolmitriptan and amitriptyline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Avoid St.John's Wort.
  • Take with food to reduce irritation.

Targets

1. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

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
  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

2. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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
  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
  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
  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
  5. Kalia M: Neurobiological basis of depression: an update. Metabolism. 2005 May;54(5 Suppl 1):24-7. Pubmed
  6. 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
  7. 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

3. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

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

4. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

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

5. Delta-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Delta-type opioid receptor P41143 Details

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. Epub 2009 Oct 14. Pubmed

6. Kappa-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Kappa-type opioid receptor P41145 Details

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. Epub 2009 Oct 14. Pubmed

7. High affinity nerve growth factor receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
High affinity nerve growth factor receptor P04629 Details

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. Pubmed

8. BDNF/NT-3 growth factors receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
BDNF/NT-3 growth factors receptor Q16620 Details

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. Pubmed

9. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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
  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. Epub 2010 Apr 2. Pubmed

10. Alpha-1D adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1D adrenergic receptor P25100 Details

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. Epub 2010 Apr 2. Pubmed

11. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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
  2. 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

12. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

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

13. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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

14. Muscarinic acetylcholine receptor M2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

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

15. Muscarinic acetylcholine receptor M3

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

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

16. Muscarinic acetylcholine receptor M4

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M4 P08173 Details

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

17. Muscarinic acetylcholine receptor M5

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M5 P08912 Details

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

18. Potassium voltage-gated channel subfamily KQT member 2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily KQT member 2 O43526 Details

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

19. Potassium voltage-gated channel subfamily A member 1

Kind: protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily A member 1 Q09470 Details

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

20. Potassium voltage-gated channel subfamily D member 2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily D member 2 Q9NZV8 Details

References:

  1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. Pubmed

21. Potassium voltage-gated channel subfamily D member 3

Kind: protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily D member 3 Q9UK17 Details

References:

  1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. Pubmed

22. Histamine H2 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: blocker

Components

Name UniProt ID Details
Histamine H2 receptor P25021 Details

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

23. Histamine H4 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Histamine H4 receptor Q9H3N8 Details

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

24. Sigma non-opioid intracellular receptor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Sigma non-opioid intracellular receptor 1 Q99720 Details

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
  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

25. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Di Matteo V, De Blasi A, Di Giulio C, Esposito E: Role of 5-HT receptors in the control of central dopamine function. Trends Pharmacol Sci. 2001 May;22(5):229-32. Pubmed

26. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

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

27. 5-hydroxytryptamine receptor 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 7 P34969 Details

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

28. 5-hydroxytryptamine receptor 1D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1D P28221 Details

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

29. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. Wahlstrom A, Lenhammar L, Ask B, Rane A: Tricyclic antidepressants inhibit opioid receptor binding in human brain and hepatic morphine glucuronidation. Pharmacol Toxicol. 1994 Jul;75(1):23-7. Pubmed
  2. 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

30. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

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

31. 5-hydroxytryptamine receptor 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 6 P50406 Details

References:

  1. Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW: Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem. 1996 Jan;66(1):47-56. Pubmed
  2. 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

32. Potassium voltage-gated channel subfamily KQT member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily KQT member 3 O43525 Details

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

33. Beta adrenergic receptor

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details
Beta-2 adrenergic receptor P07550 Details
Beta-3 adrenergic receptor P13945 Details

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

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. Pubmed
  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. Epub 2008 Feb 14. Pubmed
  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
  4. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  5. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  6. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  7. 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

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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. Epub 2008 Feb 14. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Information Hyperlinked Over Proteins (iHOP) – Website
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  6. 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

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. 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

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. 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

5. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2008 Feb 14. Pubmed
  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
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. 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

6. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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. Epub 2008 Feb 14. Pubmed

7. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  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

8. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  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

9. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

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
  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

2. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

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
  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. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
  2. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09