AMOXAPINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H16ClN3O
Molecular Weight	313.781
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC2=C(OC3=C(C=CC=C3)N=C2N4CCNCC4)C=C1

InChI

InChIKey=QWGDMFLQWFTERH-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C17H16ClN3O
Molecular Weight	313.781
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf

Amoxapine is an antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzazepines, dibenzocycloheptenes, and dibenzoxepines. It is designated chemically as 2-Chloro-11- (1-piperazinyl)dibenz[b,f ][1,4]oxazepine. Amoxapine is an antidepressant with 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 norepinephrine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Amoxapine is absorbed rapidly and reaches peak blood levels approximately 90 minutes after ingestion. It is almost completely metabolized. The main route of excretion is the kidney. In vitro tests show that amoxapine binding to human serum is approximately 90%. In man, amoxapine serum concentration declines with a half-life of eight hours. However, the major metabolite, 8-hydroxyamoxapine, has a biologic half-life of 30 hours. Metabolites are excreted in the urine in conjugated form as glucuronides. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine. The initial clinical effect may occur within four to seven days and occurs within two weeks in over 80% of responders.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine receptor 58 Target ID: CHEMBL2096905 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf	Antagonist 2737
Norepinephrine transporter 183 Target ID: CHEMBL222 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf	Inhibitor 8146
Serotonin transporter 172 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15655900	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neurotic or reactive depressive disorders 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf	Primary		Approved 8307	AMOXAPINE Approved Use Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation. Launch Date 7.1487357E11
Psychotic depressions 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf	Primary		Approved 8307	AMOXAPINE Approved Use Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation. Launch Date 7.1487357E11

C_max

Value	Dose	Co-administered	Analyte	Population
33.55 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3997304/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AMOXAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
319 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3997304/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AMOXAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.02 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3997304/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AMOXAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3997304/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AMOXAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
300 mg 1 times / day steady, oral Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf	unhealthy Health Status: unhealthy Condition: depression Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf	Other AEs: Ataxia, Drowsiness... Other AEs: Ataxia (>1) Drowsiness (14%) Dry mouth (14%) Constipation (12%) Blurred vision (7%) Anxiety (>1) Insomnia (>1) Nervousness (>1) Nightmare (>1) Restlessness (>1) Palpitations (>1) Tremor (>1) Confusion (>1) Excitement (>1) Edema (>1) Skin rash (>1) Prolactin increased (>1) Nausea (>1) Dizziness (>1) Headache (>1) Fatigue (>1) Weakness (>1) Appetite excessive (>1) Perspiration excessive (>1) Accommodation disturbance (<1%) Mydriasis (<1%) Micturition disorder (<1%) Urinary retention (<1%) Nasal stuffiness (<1%) Hypotension (<1%) Hypertension (<1%) Syncope (<1%) Tachycardia (<1%) Drug fever (<1%) Urticaria (<1%) Photosensitized (<1%) Pruritus (<1%) Vasculitis (<1%) Hepatitis (<1%) Tingling (<1%) Tinnitus (<1%) Disorientation (<1%) Seizures (<1%) Hypomania (<1%) Numbness (<1%) Incoordination (<1%) Concentration impairment (<1%) Hyperthermia (<1%) Extrapyramidal symptoms (<1%) Tardive dyskinesia (<1%) Leukopenia (<1%) Agranulocytosis (<1%) Epigastric distress (<1%) Vomiting (<1%) Flatulence (<1%) Abdominal pain (<1%) Taste peculiar (<1%) Diarrhea (<1%) Impotence (<1%) Menstrual irregularity (<1%) Breast enlargement (<1%) Inappropriate antidiuretic hormone secretion (<1%) Galactorrhea (<1%) Lacrimation (<1%) Weight gain (<1%) Weight loss (<1%) Impaired liver function (<1%) Painful ejaculation (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1168	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072691s036lbl.pdf Page: 2.0	likely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://pubmed.ncbi.nlm.nih.gov/20229012/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2675	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2675
ChemicalBook	CB5375947	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5375947
MolPort	MolPort-003-666-768	https://www.molport.com/shop/molecule-link/MolPort-003-666-768
ZINC	ZINC000000000931	http://zinc15.docking.org/substances/ZINC000000000931
eMolecules	533809	https://www.emolecules.com/cgi-bin/more?vid=533809

PubMed

Title	Date	PubMed
Amoxapine-associated acute renal failure.	1985 Jun	4002015
Amoxapine-induced cognitive impairment in two patients.	1987 Apr	3558331
Acute myocardial failure following amoxapine intoxication.	1988 Feb	3351008
Meta-analytical studies on new antidepressants.	2001	11719915
Availability of learned helplessness test as a model of depression compared to a forced swimming test in rats.	2001	11598420
[Delusional depression].	2001 Aug	11519156
Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine.	2001 Dec 27	11743975
Further characterization of 5-HT1A receptors in the goldfish retina: role of cyclic AMP in the regulation of the in vitro outgrowth of retinal explants.	2001 Mar	11495544
Glycine is taken up through GLYT1 and GLYT2 transporters into mouse spinal cord axon terminals and causes vesicular and carrier-mediated release of its proposed co-transmitter GABA.	2001 Mar	11259500
Painful ejaculation and urinary hesitancy in association with antidepressant therapy: relief with tamsulosin.	2002 Aug	12126873
The effects of tricyclic antidepressants on breast cancer risk.	2002 Jan 7	11857018
Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns.	2004 Apr 27	15109398
Risk of fetal exposure to tricyclic antidepressants.	2004 Oct	15507199
The pharmacological management of depression.	2005	16156378
Amoxapine as an atypical antipsychotic: a comparative study vs risperidone.	2005 Dec	15956984
Facilitation of spontaneous glutamate release by antidepressant drugs in rat locus coeruleus.	2005 Feb 10	15644283
Detection and treatment of akathisia in advanced cancer patients during adjuvant analgesic therapy with tricyclic antidepressants: case reports and review of the literature.	2007 Dec	18044419
Amoxapine as an antipsychotic: comparative study versus haloperidol.	2007 Dec	18004123
A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs.	2007 Mar	17150394
Differential distribution of glycine transporters in Müller cells and neurons in amphibian retinas.	2007 Mar-Apr	17640406
Prevalence and predictors of antidepressant use in a cohort of pregnant women.	2007 Sep	17565615
An autopsy case of poisoning with ethanol and psychotropic drugs.	2008 Apr	18819217
Functional expression of the glycine transporter 1 on bullfrog retinal cones.	2008 Nov 19	18841092
Amoxapine-induced tardive dyskinesia.	2009 Oct-Dec	20048464
A new strategy for antidepressant prescription.	2010	21151361
Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes.	2010 Jan	19828880
Drug-drug interaction between oxycodone and adjuvant analgesics in blood-brain barrier transport and antinociceptive effect.	2010 Jan	19499573
Tricyclic antidepressants and headaches: systematic review and meta-analysis.	2010 Oct 20	20961988

Patents

Sample Use Guides

In Vivo Use Guide

Usual effective dosage is 200 to 300 mg daily. Three weeks constitutes an adequate period of trial providing dosage has reached 300 mg daily (or lower level of tolerance) for at least two weeks. If no response is seen at 300 mg, dosage may be increased, depending upon tolerance, up to 400 mg daily.

Route of Administration: Oral

In Vitro Use Guide

Cells (mouse cortical neurons) were incubated with or without amoxapine varying concentrations of 10, 50, and 100 uM. At a concentration of 10 to 500 uM, amoxapine reversibly inhibited I(K) in a dose-dependent manner and modulated both steady-state activation and inactivation properties.

Substance Class	Chemical Created by `admin` on `Sat Dec 17 01:42:53 UTC 2022` Edited by `admin` on `Sat Dec 17 01:42:53 UTC 2022`
Record UNII	R63VQ857OT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMOXAPINE

Official Name

English

AMOXAPINE [USP MONOGRAPH]

Common Name

English

AMOXAPINE [VANDF]

Common Name

English

2-CHLORO-11-(1-PIPERAZINYL)DIBENZ(B,F)(1,4)OXAZEPINE

Systematic Name

English

NSC-759559

Code

English

CL-67,772

Code

English

DIBENZ(B,F)(1,4)OXAZEPINE, 2-CHLORO-11-(1-PIPERAZINYL)-

Systematic Name

English

amoxapine [INN]

Common Name

English

AMOXAPINE [USP-RS]

Common Name

English

CL 67772

Code

English

Amoxapine [WHO-DD]

Common Name

English

CL 67,772

Code

English

AMOXAPINE [MI]

Common Name

English

AMOXAPINE [JAN]

Common Name

English

LOXAPINE SUCCINATE IMPURITY, AMOXAPINE- [USP IMPURITY]

Common Name

English

AMOXAPINE [ORANGE BOOK]

Common Name

English

ASENDIN

Brand Name

English

AMOXAPINE [MART.]

Common Name

English

AMOXAPINE [USAN]

Common Name

English

AMOXAPINE [USP IMPURITY]

Common Name

English

CL-67772

Code

English

Classification Tree Code System Code

WHO-VATC

QN06AA17