Identification

Name
Amoxapine
Accession Number
DB00543  (APRD00142)
Type
Small Molecule
Groups
Approved
Description

Amoxapine, the N-demethylated derivative of the antipsychotic agent loxapine, is a dibenzoxazepine-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, amoxapine does not affect mood or arousal, but may cause sedation. In depressed individuals, amoxapine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs 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. Amoxapine may be used to treat neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation.

Structure
Thumb
Synonyms
  • 2-Chloro-11-(1-piperazinyl)dibenz(b,F)(1,4)oxazepine
  • Amoxapin
  • Amoxapina
  • Amoxapinum
  • Amoxepine
  • Desmethylloxapin
External IDs
CL 67,772 / CL 67772 / CL-67,772 / CL-67772
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Asendin - Tab 100mgTablet100 mgOralWyeth Ayerst Canada Inc.1999-04-122002-06-10Canada
Asendin - Tab 25mgTablet25 mgOralWyeth Ayerst Canada Inc.1997-02-042000-08-02Canada
Asendin - Tab 50mgTablet50 mgOralWyeth Ayerst Canada Inc.1997-04-292001-12-12Canada
Asendin Tab 100mgTablet100 mgOralLederle Cyanamid Canada Inc.1981-12-311999-04-12Canada
Asendin Tab 25mgTablet25 mgOralLederle Cyanamid Canada Inc.1981-12-311997-08-14Canada
Asendin Tab 50mgTablet50 mgOralLederle Cyanamid Canada Inc.1981-12-311999-04-12Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmoxapineTablet100 mg/1OralActavis Pharma Company1992-08-28Not applicableUs
AmoxapineTablet50 mg/1OralPhysicians Total Care, Inc.2011-05-12Not applicableUs
AmoxapineTablet50 mg/1OralActavis Pharma Company1992-08-28Not applicableUs
AmoxapineTablet150 mg/1OralActavis Pharma Company1992-08-28Not applicableUs
AmoxapineTablet25 mg/1OralActavis Pharma Company1992-08-28Not applicableUs
International/Other Brands
Adisen (Kun Wha) / Amolife / Amoxan (Wyeth KK) / Asendin / Asendis / Défanyl (Eisai) / Demolox (Wyeth) / Oxamine (Psyco Remedies) / Oxcap
Categories
UNII
R63VQ857OT
CAS number
14028-44-5
Weight
Average: 313.781
Monoisotopic: 313.098189856
Chemical Formula
C17H16ClN3O
InChI Key
QWGDMFLQWFTERH-UHFFFAOYSA-N
InChI
InChI=1S/C17H16ClN3O/c18-12-5-6-15-13(11-12)17(21-9-7-19-8-10-21)20-14-3-1-2-4-16(14)22-15/h1-6,11,19H,7-10H2
IUPAC Name
13-chloro-10-(piperazin-1-yl)-2-oxa-9-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3,5,7,9,12,14-heptaene
SMILES
ClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C1

Pharmacology

Indication

For the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. May also be used to treat depression accompanied by anxiety or agitation.

Associated Conditions
Pharmacodynamics

Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine

Mechanism of action

Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

TargetActionsOrganism
USodium-dependent noradrenaline transporter
inhibitor
Human
ASodium-dependent serotonin transporter
inhibitor
Human
UD(2) dopamine receptor
antagonist
Human
UD(1A) dopamine receptor
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UGamma-aminobutyric acid receptor subunit alpha-1
antagonist
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 2C
antagonist
Human
U5-hydroxytryptamine receptor 6
antagonist
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
UD(3) dopamine receptor
antagonist
Human
UD(4) dopamine receptor
antagonist
Human
UHistamine H1 receptor
antagonist
Human
UAlpha-1 adrenergic receptors
antagonist
Human
UMuscarinic acetylcholine receptor
antagonist
Human
U5-hydroxytryptamine receptor 2B
antagonist
Human
U5-hydroxytryptamine receptor 3A
antagonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
U5-hydroxytryptamine receptor 1B
antagonist
Human
UAlpha-2 adrenergic receptors
antagonist
Human
UHistamine H4 receptor
binder
Human
UGABA-A receptor (anion channel)
binder
Human
USodium-dependent dopamine transporter
binder
Human
Absorption

Rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single dose.

Volume of distribution

Widely distributed in body tissues with highest concentrations found in lungs, spleen, kidneys, heart, and brain. Lower concentrations can be detected in testes and muscle.

Protein binding

In vitro tests show that amoxapine binding to human plasma proteins is approximately 90%.

Metabolism

Amoxapine is almost completely metabolized in the liver to its major metabolite, 8-hydroxyamoxapine, and a minor metabolite, 7-hydroxyamoxapine. Both metabolites are phamacologically inactive and have half-lives of approximately 30 and 6.5 hours, respectively.

Route of elimination

60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine.

Half life

8 hours

Clearance
Not Available
Toxicity

Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects, particularly grand mal convulsions, occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Renal failure may develop two to five days after toxic overdose in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomuolysis and myolobinurla is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when Amoxapine is combined with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
(R)-warfarinThe risk or severity of adverse effects can be increased when Amoxapine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Amoxapine is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of Amoxapine can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedioneAmoxapine may decrease the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Amoxapine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Amoxapine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Amoxapine is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe risk or severity of Cardiac Arrhythmia and CNS stimulation can be increased when 3,5-diiodothyropropionic acid is combined with Amoxapine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Amoxapine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

References

Synthesis Reference

Howell, C.F., Hardy, R.A., Jr. and Quinones, N.Q.; US. Patent 3,663,696; May 16, 1972; assigned to American Cyanamid Company Howell, C.F., Hardy, R.A., Jr. and Quinones, N.Q.; U.S. Patent 3,681,357; August 1, 1972; assigned to American Cyanamid Company

US3663696
General References
Not Available
External Links
Human Metabolome Database
HMDB0014683
KEGG Drug
D00228
PubChem Compound
2170
PubChem Substance
46509117
ChemSpider
2085
BindingDB
22870
ChEBI
2675
ChEMBL
CHEMBL1113
Therapeutic Targets Database
DAP001149
PharmGKB
PA448405
IUPHAR
201
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amoxapine
ATC Codes
N06AA17 — Amoxapine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Sandoz inc
  • Watson laboratories inc
  • Lederle laboratories div american cyanamid co
Packagers
  • Kaiser Foundation Hospital
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmaceutical Utilization Management Program VA Inc.
  • Stat Rx Usa
  • United Research Laboratories Inc.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral100 mg/1
TabletOral150 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
TabletOral100 mg
TabletOral25 mg
TabletOral50 mg
Prices
Unit descriptionCostUnit
Amoxapine 30 150 mg tablet Bottle82.15USD bottle
Amoxapine 150 mg tablet2.63USD tablet
Amoxapine 100 mg tablet1.7USD tablet
Amoxapine 50 mg tablet1.02USD tablet
Amoxapine 25 mg tablet0.63USD 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)175-176Howell, C.F., Hardy, R.A., Jr. and Quinones, N.Q.; US. Patent 3,663,696; May 16, 1972; assigned to American Cyanamid Company Howell, C.F., Hardy, R.A., Jr. and Quinones, N.Q.; U.S. Patent 3,681,357; August 1, 1972; assigned to American Cyanamid Company
logP3.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.171 mg/mLALOGPS
logP2.82ALOGPS
logP3.08ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area36.86 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity89.82 m3·mol-1ChemAxon
Polarizability32.82 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier+0.988
Caco-2 permeable-0.5488
P-glycoprotein substrateSubstrate0.8068
P-glycoprotein inhibitor IInhibitor0.7622
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterInhibitor0.6414
CYP450 2C9 substrateNon-substrate0.7682
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5168
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5472
Ames testNon AMES toxic0.7277
CarcinogenicityNon-carcinogens0.8159
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9781 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6376
hERG inhibition (predictor II)Inhibitor0.7874
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-052b-4490000000-6bbd0d2c0c8fe332c636
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/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-044i-0169000000-d1665f2e6d27a9efaa39
MS/MS Spectrum - , positiveLC-MS/MSsplash10-002f-0940000000-9bf5c13f1f2b9b04f465
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dl-2690000000-0e598ca107ca857b8f06

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzoxazepines. These are compounds containing a dibenzoxazepine moiety, which consists of two benzene connected by an oxazepine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzoxazepines
Sub Class
Dibenzoxazepines
Direct Parent
Dibenzoxazepines
Alternative Parents
Diarylethers / Piperazines / Imidolactams / Benzenoids / Aryl chlorides / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds / Dialkylamines / Carboxamidines / Azacyclic compounds
show 3 more
Substituents
Dibenzoxazepine / Diaryl ether / Aryl chloride / Aryl halide / 1,4-diazinane / Piperazine / Imidolactam / Benzenoid / Amidine / Carboxylic acid amidine
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dibenzooxazepine (CHEBI:2675)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. 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
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. Spurlock G, Buckland P, O'Donovan M, McGuffin P: Lack of effect of antidepressant drugs on the levels of mRNAs encoding serotonergic receptors, synthetic enzymes and 5HT transporter. Neuropharmacology. 1994 Mar-Apr;33(3-4):433-40. [PubMed:7984281]
  2. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. Wei HB, Niu XY: [Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]. Yao Xue Xue Bao. 1990;25(12):881-5. [PubMed:1966571]
  2. Nasu R, Matsuo H, Takanaga H, Ohtani H, Sawada Y: Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice. Biopharm Drug Dispos. 2000 May;21(4):129-38. [PubMed:11180191]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Nasu R, Matsuo H, Takanaga H, Ohtani H, Sawada Y: Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice. Biopharm Drug Dispos. 2000 May;21(4):129-38. [PubMed:11180191]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881]
  2. Buckley NA, McManus PR: Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998 May;18(5):369-81. [PubMed:9589848]
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
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Wei HB, Niu XY: [Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]. Yao Xue Xue Bao. 1990;25(12):881-5. [PubMed:1966571]
  2. Buckley NA, McManus PR: Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998 May;18(5):369-81. [PubMed:9589848]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Richelson E: Antimuscarinic and other receptor-blocking properties of antidepressants. Mayo Clin Proc. 1983 Jan;58(1):40-6. [PubMed:6130192]
  2. Buckley NA, McManus PR: Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998 May;18(5):369-81. [PubMed:9589848]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
References
  1. Buckley NA, McManus PR: Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998 May;18(5):369-81. [PubMed:9589848]
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. Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J: Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996 Aug;126(3):234-40. [PubMed:8876023]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Glusa E, Pertz HH: Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors. Br J Pharmacol. 2000 Jun;130(3):692-8. [PubMed:10821800]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
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
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
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. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR: Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther. 2005 Dec;315(3):1278-87. Epub 2005 Aug 31. [PubMed:16135699]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
Details
14. D(4) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR: Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther. 2005 Dec;315(3):1278-87. Epub 2005 Aug 31. [PubMed:16135699]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881]
Kind
Protein group
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...

Components:
References
  1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
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...

Components:
References
  1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Glusa E, Pertz HH: Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors. Br J Pharmacol. 2000 Jun;130(3):692-8. [PubMed:10821800]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated potassium channel 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. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Gozlan H, Saddiki-Traki F, Merahi N, Laguzzi R, Hamon M: [Preclinical pharmacology of amoxapine and amitriptyline. Implications of serotoninergic and opiodergic systems in their central effect in rats]. Encephale. 1991 Dec;17 Spec No 3:415-22. [PubMed:1666997]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. 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. Gozlan H, Saddiki-Traki F, Merahi N, Laguzzi R, Hamon M: [Preclinical pharmacology of amoxapine and amitriptyline. Implications of serotoninergic and opiodergic systems in their central effect in rats]. Encephale. 1991 Dec;17 Spec No 3:415-22. [PubMed:1666997]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Gozlan H, Saddiki-Traki F, Merahi N, Laguzzi R, Hamon M: [Preclinical pharmacology of amoxapine and amitriptyline. Implications of serotoninergic and opiodergic systems in their central effect in rats]. Encephale. 1991 Dec;17 Spec No 3:415-22. [PubMed:1666997]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

Components:
References
  1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881]
Details
23. Histamine H4 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Histamine receptor activity
Specific Function
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agoni...
Gene Name
HRH4
Uniprot ID
Q9H3N8
Uniprot Name
Histamine H4 receptor
Molecular Weight
44495.375 Da
References
  1. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R: Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21. Epub 2005 Jun 9. [PubMed:15947036]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Wei HB, Niu XY: [Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]. Yao Xue Xue Bao. 1990;25(12):881-5. [PubMed:1966571]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
  2. PDSP Ki Database [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Shin HC, Kim HR, Cho HJ, Yi H, Cho SM, Lee DG, Abd El-Aty AM, Kim JS, Sun D, Amidon GL: Comparative gene expression of intestinal metabolizing enzymes. Biopharm Drug Dispos. 2009 Nov;30(8):411-21. doi: 10.1002/bdd.675. [PubMed:19746353]

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]

Drug created on June 13, 2005 07:24 / Updated on October 10, 2018 21:44