Identification

Name
Imipramine
Accession Number
DB00458  (APRD00672, DB08002)
Type
Small Molecule
Groups
Approved
Description

Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative 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, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. 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 [5]. Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. Imipramine may be used to treat depression and nocturnal enuresis in children [Label]. Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD) [12, 11, 1, 13, 14, 15, 2].

Structure
Thumb
Synonyms
  • 10,11-dihydro-N,N-Dimethyl-5H-dibenz[b,F]azepine-5-propanamine
  • 3-(5H-DIBENZO[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine
  • 5-[3-(dimethylamino)Propyl]-10,11-dihydro-5H-dibenz[b,F]azepine
  • Antideprin
  • Imipramin
  • Imipramina
  • Imipramine
  • Imipraminum
  • Imizine
  • Irmin
  • Melipramine
  • N-(gamma-Dimethylaminopropyl)iminodibenzyl
  • N-(γ-dimethylaminopropyl)iminodibenzyl
External IDs
NSC-169866 / ORG-2463
Product Ingredients
IngredientUNIICASInChI Key
Imipramine HydrochlorideBKE5Q1J60U113-52-0XZZXIYZZBJDEEP-UHFFFAOYSA-N
Imipramine PamoateMC34P3029810075-24-8SBDXQUVAAJKLDH-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ImipramineTablet10 mgOralAa Pharma Inc1976-12-31Not applicableCanada
ImipramineTablet75 mgOralAa Pharma Inc1989-12-31Not applicableCanada
ImipramineTablet50 mgOralAa Pharma Inc1975-12-31Not applicableCanada
ImipramineTablet25 mgOralAa Pharma Inc1975-12-31Not applicableCanada
Imipramine 10tabTablet10 mgOralPro Doc Limitee1976-12-312010-07-13Canada
Imipramine 25tabTablet25 mgOralPro Doc Limitee1976-12-312010-07-13Canada
Imipramine 50 Tab 50mgTablet50 mgOralPro Doc Limitee1978-12-312010-07-13Canada
Imipramine Hydrochloride Tablets 25mgTablet25 mgOralD.C. Labs Limited1977-12-312003-07-11Canada
Imipramine Hydrochloride Tablets 50mgTablet50 mgOralD.C. Labs Limited1977-12-312003-07-11Canada
Imipramine PamoateCapsule150 mg/1OralMallinckrodt2009-10-152016-12-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-imipramineTablet75 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-imipramineTablet10 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-imipramineTablet50 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-imipramineTablet25 mgOralApotex CorporationNot applicableNot applicableCanada
Imipramine HydrochlorideTablet10 mg/1OralCarilion Materials Management1983-10-21Not applicableUs
Imipramine HydrochlorideTablet, film coated25 mg/1OralRemedy Repack2007-11-192018-10-22Us
Imipramine HydrochlorideTablet, film coated50 mg/1OralAv Kare, Inc.2015-12-09Not applicableUs
Imipramine HydrochlorideTablet, film coated50 mg/1OralExcellium Pharmaceutical, Inc.2012-11-01Not applicableUs
Imipramine HydrochlorideTablet, film coated25 mg/1OralSun Pharmaceutical Industries Limited1990-06-052020-12-31Us53489 0331 01 nlmimage10 17078bdc
Imipramine HydrochlorideTablet, film coated10 mg/1OralRichmond Pharmaceuticals1990-06-052020-12-31Us
International/Other Brands
Antidep (Torrent) / Depsonil (Abbott) / Depsonil-PM (Abbott) / Elamin (Baroda) / Fronil (Johnson) / Imidol (Tanabe Mitsubishi Pharma) / Imipramin Dak (Nycomed) / Imiprex (Dumex) / Pramin (Incepta)
Categories
UNII
OGG85SX4E4
CAS number
50-49-7
Weight
Average: 280.4073
Monoisotopic: 280.193948778
Chemical Formula
C19H24N2
InChI Key
BCGWQEUPMDMJNV-UHFFFAOYSA-N
InChI
InChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3
IUPAC Name
(3-{2-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)dimethylamine
SMILES
CN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12

Pharmacology

Indication

For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older [Label].

May also be used off-label to manage panic disorders with or without agoraphobia, as a second line agent for ADHD in children and adolescents, to manage bulimia nervosa, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, for the treatment of acute stress disorder and posttraumatic stress disorder, and for symptomatic treatment of postherpetic neuralgia and painful diabetic neuropathy [12, 11, 1, 13, 14, 15, 2].

Associated Conditions
Pharmacodynamics

Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. While it acts to block both, imipramine displays a much higher affinity for the serotonin reuptake transporter than for the norepinephrine reuptake transporter [5]. Imipramine produces effects similar to other monoamine targeting antidepressants, increasing serotonin- and norepinephrine-based neurotransmission.

This modulation of neurotransmission produces a complex range of changes in brain structure and function along with an improvement in depressive symptoms. The changes include increases in hippocampal neurogenesis and reduced downregulation of this neurogenesis in response to stress [6]. These implicate brain derived neurotrophic factor signalling as a necessary contributor to antidepressant effect although the link to the direct increase in monoamine neurotransmission is unclear.

Serotonin reuptake targeting agents may also produce a down-regulation in β-adrenergic receptors in the brain [8].

Mechanism of action

Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin [5, 10]. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin [7]. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signalling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression [9].

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
inhibitor
Human
ASodium-dependent serotonin transporter
inhibitor
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
NHistamine H1 receptor
antagonist
Human
NAlpha-1A adrenergic receptor
antagonist
Human
NAlpha-1D adrenergic receptor
antagonist
Human
NMuscarinic acetylcholine receptor M1
antagonist
Human
NMuscarinic acetylcholine receptor M2
antagonist
Human
NMuscarinic acetylcholine receptor M3
antagonist
Human
NMuscarinic acetylcholine receptor M4
antagonist
Human
NMuscarinic acetylcholine receptor M5
antagonist
Human
NPotassium voltage-gated channel subfamily D member 2
inhibitor
Human
NPotassium voltage-gated channel subfamily D member 3
inhibitor
Human
U5-hydroxytryptamine receptor 2C
antagonist
binder
Human
UAlpha-1B adrenergic receptor
antagonist
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
UD(1) dopamine receptor
binder
Human
UD(2) dopamine receptor
binder
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
USodium-dependent dopamine transporter
inhibitor
Human
U5-hydroxytryptamine receptor 1A
activator
Human
U5-hydroxytryptamine receptor 6
binder
Human
UPotassium voltage-gated channel subfamily H member 1Not AvailableHuman
UAlpha-1-acid glycoprotein 2Not AvailableHuman
Absorption

Rapidly and well absorbed (>95%) after oral administration [3]. The primary site of absorption is the small intestine as the basic amine groups are ionized in the acidic environment of the stomach, preventing movement across tissues. Bioavailability ranges from 29-77% due to high inter-individual variability. Peak plasma concentration is usually attained 2-6 hours following oral administration. Absorption is unaffected by food.

Volume of distribution

Imipramine has a high apparent volume of distribution of 10-20 L/kg [3]. The drug is known to accumulate in the brain at concentrations 30-40 times that in systemic circulation.

Protein binding

Imipramine is 60-96% bound to plasma proteins in circulation [3]. It is known to bind albumin, α1-acid glycoprotein, and lipoproteins.

Metabolism

Imipramine is nearly exclusively metabolized by the liver [3]. Imipramine is converted to desipramine by CYP1A2, CYP3A4, CYP2C19. Both imipramine and desipramine are hydroxylated by CYP2D6 [4]. Desipramine is an active metabolite.

Minor metabolic pathways include dealkylation to form an imidodibenzyl product as well as demethylation of desipramine to didemethylimipramine and subsequent hydroxylation [3].

Less than 5% of orally administered imipramine is excreted unchanged.

Route of elimination

Imipramine is primarily excreted in the urine with less than 5% present as the parent compound [3]

Half life

Imipramine has a mean half life of 12 h. Its active metabolite, desipramine has a mean half life of 22.5 h [3].

Clearance

Imipramine has a mean clearance of 1 L/h/kg. Its active metabolite, desipramine has a mean clearance of 1.8 L/h/kg [3].

Toxicity

The anticholinergic actvity of imipramine can produce dry mucous membranes, blurred vision, increased intraocular pressure, hyperthermia, constipation, adynamic ileus, urinary retention, delayed micturition, and dilation of the urinary tract [16].

Central nervous system and neuromuscular effects include drowsiness, lethargy, fatigue, agitation, excitement, nightmares, restlessness, insomnia, confusion, disturbed concentration, disorientation, delusions, and hallucinations.

Effects on the GI tract include anorexia, nausea and vomiting, diarrhea, abdominal cramps, increases in pancreatic enzymes, epigastric distress, stomatitis, peculiar taste, and black tongue.

Rarely agranulocytosis, thrombocytopenia, eosinophilia, leukopenia, and purpura have occured.

Infants whose mothers were receiving tricyclic antidepressants prior to delivery have experienced cardiac problems, irritability, respiratory distress, muscle spasms, seizures, and urinary retention.

Serotonin syndrome can occur when used in conjunction with other pro-serotonergic drugs.

LD50 Values

Rat - Oral 250 mg/kg - Intraperitoneal 79mg/kg - Subcutaneous 250 mg/kg - Intravenous 15.9 mg/kg

Mouse - Oral 188 mg/kg - Intraperitoneal 51.6 mg/kg - Subcutaneous 195 μg/kg - Intravenous 21 mg/kg

Human range of toxicity is considered to include single dosages greater than 5 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Imipramine Action PathwayDrug action
Imipramine Metabolism PathwayDrug metabolism
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 imipramine.Details
Cytochrome P450 2D6CYP2D6*3Not Available2549delAEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of imipramine.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableA alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of imipramine.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of imipramine.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of imipramine.Details
Cytochrome P450 2C19CYP2C19*2Not Available681G>AEffect Directly StudiedThe presence of this polymorphism in CYP2C19 is associated with poor metabolism of imipramine.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AEffect Directly StudiedThe presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of imipramine.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, 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, 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, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, 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, 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, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, 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, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, 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, 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, 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, dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, 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, 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, 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 2D6CYP2D6*3Not AvailableG alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of imipramine.Details
Cytochrome P450 2D6CYP2D6*4Not Available3877G>AEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of imipramine.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Imipramine can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Imipramine can be decreased when combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of Imipramine can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedioneImipramine may decrease the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Imipramine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Imipramine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Imipramine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Imipramine is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of Imipramine can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Imipramine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Avoid St.John's Wort.
  • Do not take fibers at the same time.
  • Take with food.

References

Synthesis Reference

U.S. Patent 2,554,736.

General References
  1. Authors unspecified: Treatment of patients with eating disorders,third edition. American Psychiatric Association. Am J Psychiatry. 2006 Jul;163(7 Suppl):4-54. [PubMed:16925191]
  2. Low PA, Dotson RM: Symptomatic treatment of painful neuropathy. JAMA. 1998 Dec 2;280(21):1863-4. [PubMed:9846782]
  3. Sallee FR, Pollock BG: Clinical pharmacokinetics of imipramine and desipramine. Clin Pharmacokinet. 1990 May;18(5):346-64. [PubMed:2185906]
  4. Gardiner SJ, Begg EJ: Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev. 2006 Sep;58(3):521-90. doi: 10.1124/pr.58.3.6. [PubMed:16968950]
  5. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [PubMed:17471183]
  6. Schmidt HD, Duman RS: The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol. 2007 Sep;18(5-6):391-418. doi: 10.1097/FBP.0b013e3282ee2aa8. [PubMed:17762509]
  7. Heninger GR, Delgado PL, Charney DS: The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry. 1996 Jan;29(1):2-11. doi: 10.1055/s-2007-979535. [PubMed:8852528]
  8. Wamsley JK, Byerley WF, McCabe RT, McConnell EJ, Dawson TM, Grosser BI: Receptor alterations associated with serotonergic agents: an autoradiographic analysis. J Clin Psychiatry. 1987 Mar;48 Suppl:19-25. [PubMed:3029045]
  9. Shelton RC: Cellular mechanisms in the vulnerability to depression and response to antidepressants. Psychiatr Clin North Am. 2000 Dec;23(4):713-29. [PubMed:11147243]
  10. Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
  11. AACAP: Practice Parameter for the Assessment and Treatment of Children and Adolescents With Attention-Deficit/ Hyperactivity Disorder [Link]
  12. APA: Practice Guideline for the Treatment of Patients with Panic Disorder [Link]
  13. APA: Practice Guideline for the Treatment of Patients with Schizophrenia Second Edition [Link]
  14. APA: Practice Guideline for the Treatment of Patients with Bipolar Disorder Second Edition [Link]
  15. APA: Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder [Link]
  16. TOXNET: Imipramine [Link]
External Links
Human Metabolome Database
HMDB0001848
KEGG Compound
C07049
PubChem Compound
3696
PubChem Substance
46507351
ChemSpider
3568
BindingDB
50010859
ChEBI
47499
ChEMBL
CHEMBL11
Therapeutic Targets Database
DAP001154
PharmGKB
PA449969
IUPHAR
357
Guide to Pharmacology
GtP Drug Page
HET
IXX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Imipramine
ATC Codes
N06AA02 — Imipramine
AHFS Codes
  • 28:16.04.28 — Tricyclics and Other Norepinephrine-reuptake Inhibitors
PDB Entries
2q72 / 6g9b
FDA label
Download (495 KB)
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceIncontinence, Fecal / Urinary Incontinence,Stress1
1CompletedTreatmentDepression1
2CompletedTreatmentArrhythmia of ventricular origin / Arrythmias / Cardiovascular Disease (CVD) / Heart Diseases1
2CompletedTreatmentDepression1
2CompletedTreatmentSomatization Disorder / Somatoform Disorders1
3CompletedBasic ScienceBack Pain Lower Back1
3CompletedPreventionArrythmias / Cardiovascular Disease (CVD) / Heart Arrest / Heart Diseases / Myocardial Infarction / Ventricular Fibrillation1
3CompletedTreatmentArrhythmia of ventricular origin / Arrythmias / Cardiovascular Disease (CVD) / Death, Sudden,Cardiac / Heart Diseases / Ventricular Fibrillation / Ventricular Tachycardia (VT)1
3CompletedTreatmentFunctional Gastrointestinal Disorders / Indigestion1
3CompletedTreatmentGastro-esophageal Reflux Disease (GERD)1
3CompletedTreatmentThoracic Pain1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4CompletedTreatmentDepression1
4CompletedTreatmentDepressive Disorder NOS / Dysthymic Disorder / Major Depressive Disorder (MDD)1
4CompletedTreatmentDysthymic Disorder / Major Depressive Disorder (MDD)2
4Unknown StatusTreatmentPolyneuropathies1
Not AvailableCompletedBasic ScienceUrethral Sphincter Activity1
Not AvailableCompletedDiagnosticHealthy Volunteers1
Not AvailableCompletedTreatmentDepression1
Not AvailableCompletedTreatmentPanic Disorders1
Not AvailableNot Yet RecruitingTreatmentCancer, Breast1
Not AvailableUnknown StatusTreatmentTreatment Resistant Depression (TRD)1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • Actavis totowa llc
  • Lederle laboratories div american cyanamid co
  • Lupin ltd
  • Mutual pharmaceutical co inc
  • Par pharmaceutical inc
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Usl pharma inc
  • Vangard laboratories inc div midway medical co
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Abbott laboratories pharmaceutical products div
  • Alra laboratories inc
  • Sanofi aventis us llc
  • Tyco healthcare group lp
  • Odyssey pharmaceuticals inc
Packagers
  • Actavis Group
  • Amerisource Health Services Corp.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Ciba Geigy Ltd.
  • Comprehensive Consultant Services Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Lupin Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Prepackage Specialists
  • Professional Co.
  • Qualitest
  • Remedy Repack
  • Richmond Pharmacy
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Sun Pharmaceutical Industries Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • United Research Laboratories Inc.
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral25 mg
TabletOral50 mg
TabletOral75 mg
TabletOral10 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
CapsuleOral100 mg/1
CapsuleOral125 mg/1
CapsuleOral150 mg/1
CapsuleOral75 mg/1
Injection, solutionIntramuscular25 mg/2mL
Tablet, sugar coatedOral10 mg/1
Tablet, sugar coatedOral25 mg/1
Tablet, sugar coatedOral50 mg/1
Prices
Unit descriptionCostUnit
Tofranil-PM 30 125 mg capsule Bottle588.33USD bottle
Tofranil-PM 30 150 mg capsule Bottle588.33USD bottle
Tofranil-PM 30 75 mg capsule Bottle588.33USD bottle
Tofranil 30 50 mg tablet Bottle185.09USD bottle
Trimipramine maleate powder51.0USD g
Tofranil-pm 100 mg capsule19.23USD capsule
Tofranil-pm 150 mg capsule18.86USD capsule
Tofranil-pm 75 mg capsule18.86USD capsule
Tofranil-pm 125 mg capsule18.68USD capsule
Imipramine pamoate 75 mg capsule16.35USD capsule
Imipramine pamoate 100 mg capsule15.17USD capsule
Imipramine pamoate 125 mg capsule15.17USD capsule
Imipramine pamoate 150 mg capsule15.17USD capsule
Tofranil 50 mg tablet6.64USD tablet
Surmontil 100 mg capsule5.92USD capsule
Tofranil 25 mg tablet4.97USD tablet
Tofranil 10 mg tablet4.73USD tablet
Surmontil 50 mg capsule4.07USD capsule
Trimipramine Maleate 50 mg capsule3.27USD capsule
Trimipramine 50 mg capsule3.14USD capsule
Surmontil 25 mg capsule2.49USD capsule
Cenestin 0.3 mg tablet2.21USD tablet
Cenestin 0.45 mg tablet2.21USD tablet
Cenestin 0.625 mg tablet2.21USD tablet
Cenestin 0.9 mg tablet2.21USD tablet
Cenestin 1.25 mg tablet2.21USD tablet
Trimipramine 25 mg capsule1.92USD capsule
Apo-Trimip 100 mg Tablet0.97USD tablet
Imipramine hcl powder0.77USD g
Apo-Trimip 75 mg Capsule0.77USD capsule
Apo-Imipramine 75 mg Tablet0.58USD tablet
Tofranil 50 mg Tablet0.57USD tablet
Apo-Trimip 50 mg Tablet0.57USD tablet
Imipramine hcl 10 mg tablet0.46USD tablet
Imipramine hcl 50 mg tablet0.44USD tablet
Apo-Imipramine 50 mg Tablet0.4USD tablet
Imipramine hcl 25 mg tablet0.35USD tablet
Apo-Trimip 25 mg Tablet0.29USD tablet
Apo-Imipramine 25 mg Tablet0.25USD tablet
Apo-Trimip 12.5 mg Tablet0.23USD tablet
Apo-Imipramine 10 mg Tablet0.14USD 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)174-175U.S. Patent 2,554,736.
boiling point (°C)160 °C at 1.00E-01 mm HgPhysProp
water solubility18.2 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.80HANSCH,C ET AL. (1995)
logS-4.19ADME Research, USCD
Caco2 permeability-4.85ADME Research, USCD
pKa9.4SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0664 mg/mLALOGPS
logP4.53ALOGPS
logP4.28ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity90.61 m3·mol-1ChemAxon
Polarizability33.39 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9822
Blood Brain Barrier+0.9865
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.7684
P-glycoprotein inhibitor IInhibitor0.8662
P-glycoprotein inhibitor IIInhibitor0.6205
Renal organic cation transporterInhibitor0.8541
CYP450 2C9 substrateNon-substrate0.7799
CYP450 2D6 substrateSubstrate0.9532
CYP450 3A4 substrateSubstrate0.6718
CYP450 1A2 substrateNon-inhibitor0.7583
CYP450 2C9 inhibitorNon-inhibitor0.9089
CYP450 2D6 inhibitorInhibitor0.9017
CYP450 2C19 inhibitorNon-inhibitor0.9304
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8399
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9329
BiodegradationNot ready biodegradable0.9819
Rat acute toxicity3.0187 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9172
hERG inhibition (predictor II)Inhibitor0.7771
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10.2 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0019-7490000000-3fb4d40b6a219f088ec8
Mass Spectrum (Electron Ionization)MSsplash10-0543-8890000000-6cf8e84f007ce7c750f2
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-000i-9000000000-55d924fd00e5b357ce9e
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-000i-9000000000-eb3c0ecdffc5d9d95e33
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-0ab9-9432000000-033c51459b692622ee7d
MS/MS Spectrum - EI-B (Unknown) , PositiveLC-MS/MSsplash10-0019-7490000000-bb99ef31a755d9f6ba14
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/MSsplash10-052r-9010000000-961429188e57c1480db8
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzazepines. These are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Dibenzazepines
Direct Parent
Dibenzazepines
Alternative Parents
Alkyldiarylamines / Azepines / Benzenoids / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Dibenzazepine / Alkyldiarylamine / Tertiary aliphatic/aromatic amine / Azepine / Benzenoid / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dibenzoazepine (CHEBI:47499) / a small molecule (CPD-11438)

Targets

Kind
Protein
Organism
Human
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. Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. [PubMed:16893531]
  2. Dziedzicka-Wasylewska M, Faron-Gorecka A, Kusmider M, Drozdowska E, Rogoz Z, Siwanowicz J, Caron MG, Bonisch H: Effect of antidepressant drugs in mice lacking the norepinephrine transporter. Neuropsychopharmacology. 2006 Nov;31(11):2424-32. Epub 2006 Mar 22. [PubMed:16554743]
  3. Anton M, Wagner B, Haubner R, Bodenstein C, Essien BE, Bonisch H, Schwaiger M, Gansbacher B, Weber WA: Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells. J Gene Med. 2004 Jan;6(1):119-26. [PubMed:14716684]
  4. Kantor L, Hewlett GH, Park YH, Richardson-Burns SM, Mellon MJ, Gnegy ME: Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells. J Pharmacol Exp Ther. 2001 Jun;297(3):1016-24. [PubMed:11356924]
  5. Tatsumi M, Jansen K, Blakely RD, Richelson E: Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol. 1999 Mar 5;368(2-3):277-83. [PubMed:10193665]
Kind
Protein
Organism
Human
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. Leboyer M, Quintin P, Manivet P, Varoquaux O, Allilaire JF, Launay JM: Decreased serotonin transporter binding in unaffected relatives of manic depressive patients. Biol Psychiatry. 1999 Dec 15;46(12):1703-6. [PubMed:10624553]
  2. Scholze P, Zwach J, Kattinger A, Pifl C, Singer EA, Sitte HH: Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter. J Pharmacol Exp Ther. 2000 Jun;293(3):870-8. [PubMed:10869387]
  3. Quintin P, Benkelfat C, Launay JM, Arnulf I, Pointereau-Bellenger A, Barbault S, Alvarez JC, Varoquaux O, Perez-Diaz F, Jouvent R, Leboyer M: Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder. Biol Psychiatry. 2001 Aug 1;50(3):184-90. [PubMed:11513817]
  4. Goulet M, Miller GM, Bendor J, Liu S, Meltzer PC, Madras BK: Non-amines, drugs without an amine nitrogen, potently block serotonin transport: novel antidepressant candidates? Synapse. 2001 Dec 1;42(3):129-40. [PubMed:11746710]
  5. Barkan T, Gurwitz D, Levy G, Weizman A, Rehavi M: Biochemical and pharmacological characterization of the serotonin transporter in human peripheral blood lymphocytes. Eur Neuropsychopharmacol. 2004 May;14(3):237-43. [PubMed:15056483]
  6. Schloss P, Betz H: Heterogeneity of antidepressant binding sites on the recombinant rat serotonin transporter SERT1. Biochemistry. 1995 Oct 3;34(39):12590-5. [PubMed:7548008]
  7. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Zanoveli JM, Nogueira RL, Zangrossi H Jr: Chronic imipramine treatment sensitizes 5-HT1A and 5-HT 2 A receptors in the dorsal periaqueductal gray matter: evidence from the elevated T-maze test of anxiety. Behav Pharmacol. 2005 Nov;16(7):543-52. [PubMed:16170231]
Details
4. Histamine H1 receptor
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
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
Human
Pharmacological action
No
Actions
Antagonist
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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
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...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor 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...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
General Function
Receptor 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...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
General Function
Guanyl-nucleotide exchange factor 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...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
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...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 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]
Kind
Protein
Organism
Human
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. Mediates the major part of the dendritic A-type current I(SA) in brai...
Gene Name
KCND2
Uniprot ID
Q9NZV8
Uniprot Name
Potassium voltage-gated channel subfamily D member 2
Molecular Weight
70535.825 Da
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:9781919]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated...
Gene Name
KCND3
Uniprot ID
Q9UK17
Uniprot Name
Potassium voltage-gated channel subfamily D member 3
Molecular Weight
73450.53 Da
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:9781919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
Binder
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. 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]
  2. Roth BL: Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry. 1994 Jun;6(2):67-78. [PubMed:7804391]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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
Human
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. Roth BL: Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry. 1994 Jun;6(2):67-78. [PubMed:7804391]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

Components:
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [PubMed:9686407]
Details
18. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Peddi S, Roth BL, Glennon RA, Westkaemper RB: Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA). Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. [PubMed:15081025]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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 ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Melikian HE, Buckley KM: Membrane trafficking regulates the activity of the human dopamine transporter. J Neurosci. 1999 Sep 15;19(18):7699-710. [PubMed:10479674]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
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. Haddjeri N, Blier P, de Montigny C: Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. J Neurosci. 1998 Dec 1;18(23):10150-6. [PubMed:9822768]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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. Grimaldi B, Bonnin A, Fillion MP, Ruat M, Traiffort E, Fillion G: Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development. Naunyn Schmiedebergs Arch Pharmacol. 1998 Apr;357(4):393-400. [PubMed:9606024]
  2. Roth BL: Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry. 1994 Jun;6(2):67-78. [PubMed:7804391]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphorelay sensor kinase activity
Specific Function
Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:22732247). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (By sim...
Gene Name
KCNH1
Uniprot ID
O95259
Uniprot Name
Potassium voltage-gated channel subfamily H member 1
Molecular Weight
111421.76 Da
References
  1. Garcia-Ferreiro RE, Kerschensteiner D, Major F, Monje F, Stuhmer W, Pardo LA: Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J Gen Physiol. 2004 Oct;124(4):301-17. Epub 2004 Sep 13. [PubMed:15365094]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and ava...
Gene Name
ORM2
Uniprot ID
P19652
Uniprot Name
Alpha-1-acid glycoprotein 2
Molecular Weight
23602.43 Da
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [PubMed:8946472]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Koyama E, Chiba K, Tani M, Ishizaki T: Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210. [PubMed:9190854]
  3. Nykamp DL, Blackmon CL, Schmidt PE, Roberson AG: QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother. 2005 Mar;39(3):543-6. doi: 10.1345/aph.1E513. Epub 2005 Feb 1. [PubMed:15687478]
  4. Masubuchi Y, Takahashii C, Fujio N, Horie T, Suzuki T, Imaoka S, Funae Y, Narimatsu S: Inhibition and induction of cytochrome P450 isozymes after repetitive administration of imipramine in rats. Drug Metab Dispos. 1995 Sep;23(9):999-1003. [PubMed:8565792]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. Morinobu S, Tanaka T, Kawakatsu S, Totsuka S, Koyama E, Chiba K, Ishizaki T, Kubota T: Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy. Psychiatry Clin Neurosci. 1997 Aug;51(4):253-7. [PubMed:9316174]
  3. Madsen H, Rasmussen BB, Brosen K: Imipramine demethylation in vivo: impact of CYP1A2, CYP2C19, and CYP3A4. Clin Pharmacol Ther. 1997 Mar;61(3):319-24. [PubMed:9084457]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  5. Koyama E, Chiba K, Tani M, Ishizaki T: Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210. [PubMed:9190854]
  6. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. [PubMed:12065442]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Brosen K: Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet. 1995;29 Suppl 1:20-5. [PubMed:8846619]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Koyama E, Chiba K, Tani M, Ishizaki T: Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210. [PubMed:9190854]
  4. Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP, Maurel P, Beaune P, Leroux JP: Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol. 1993 May;43(5):827-32. [PubMed:8502233]
  5. Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO: Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7. [PubMed:8474022]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Koyama E, Chiba K, Tani M, Ishizaki T: Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210. [PubMed:9190854]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Chen H, Brzezinski MR, Fantel AG, Juchau MR: Catalysis of drug oxidation during embryogenesis in human hepatic tissues using imipramine as a model substrate. Drug Metab Dispos. 1999 Nov;27(11):1306-8. [PubMed:10534316]
Kind
Protein
Organism
Human
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. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
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. 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:2870173]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Yoo MJ, Hage DS: Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16. [PubMed:20956006]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. 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:12438524]
  2. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]
  3. 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:12954186]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [PubMed:12089365]
  2. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. [PubMed:10966924]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. [PubMed:10825452]

Drug created on June 13, 2005 07:24 / Updated on November 17, 2018 07:09