Amoxapine (CHEM002217)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (25)XML
Record Information
Version1.0
Creation Date2009-07-21 20:27:06 UTC
Update Date2016-11-09 01:08:42 UTC
Accession NumberCHEM002217
Identification
Common NameAmoxapine
ClassSmall Molecule
DescriptionAmoxapine, 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.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressant, Second-Generation
  • Antidepressive Agent, Second-Generation
  • Dopamine Antagonist
  • Drug
  • Ether
  • Metabolite
  • Neurotransmitter Uptake Inhibitor
  • Organic Compound
  • Organochloride
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
2-Chloro-11-(1-piperazinyl)dibenz(b,F)(1,4)oxazepineChEBI
AmoxapinaChEBI
AmoxapinumChEBI
DesmethylloxapinChEBI
AsendinKegg
AmoxepineHMDB
Amoxapine lederle brandHMDB
DéfanylHMDB
Cyanamid brand OF amoxapineHMDB
Amoxapine wyeth brandHMDB
AsendisHMDB
DesmethylloxapineHMDB
Amoxapine cyanamid brandHMDB
DemoloxHMDB
Lederle brand OF amoxapineHMDB
Wyeth brand OF amoxapineHMDB
Chemical FormulaC17H16ClN3O
Average Molecular Mass313.781 g/mol
Monoisotopic Mass313.098 g/mol
CAS Registry Number14028-44-5
IUPAC Name13-chloro-10-(piperazin-1-yl)-2-oxa-9-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3,5,7,9,12,14-heptaene
Traditional Nameamoxapine
SMILESClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C1
InChI IdentifierInChI=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
InChI KeyQWGDMFLQWFTERH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzoxazepines. Dibenzoxazepines are compounds containing a dibenzoxazepine moiety, which consists of two benzene connected by an oxazepine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzoxazepines
Sub ClassDibenzoxazepines
Direct ParentDibenzoxazepines
Alternative Parents
Substituents
  • Dibenzoxazepine
  • Diaryl ether
  • Aryl chloride
  • Aryl halide
  • 1,4-diazinane
  • Piperazine
  • Imidolactam
  • Benzenoid
  • Amidine
  • Carboxylic acid amidine
  • Secondary aliphatic amine
  • Oxacycle
  • Ether
  • Azacycle
  • Secondary amine
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organohalogen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Amine
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point175-176°C
Boiling PointNot Available
Solubility1.71e-01 g/L
Predicted Properties
PropertyValueSource
Water Solubility0.17 g/LALOGPS
logP2.82ALOGPS
logP3.08ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area36.86 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity89.82 m³·mol⁻¹ChemAxon
Polarizability32.82 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-6190000000-1acb98762576326ae75bSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00dl-2690000000-0e598ca107ca857b8f06Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-044i-0169000000-d1665f2e6d27a9efaa39Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-002f-0940000000-9bf5c13f1f2b9b04f465Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00dl-2690000000-0e598ca107ca857b8f06Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-006x-2950000000-2fb725746001d0be41d1Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-0006-0910000000-7df25fea8ffb96c66d50Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-03k9-1059000000-99ec364d324293ba9191Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-03di-0009000000-fb09780a1d33ba8eb3c8Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-00di-2090000000-046bbbcb38472a6b5a4cSpectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-00di-2290000000-47774f87a43619d76d34Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-00di-2290000000-53b12cd961449d9ea634Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-873be01dd22731e1f7a7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0049000000-3989b74ad41770f20ee0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01r6-9440000000-54259557a6e11d912eb7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0019000000-eaaa73a51b5bbc0bf28bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0049000000-be3ce6855a4cc094b8fcSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9250000000-d2f001cf68189e0c19d4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-c66d97d82d39ee90b585Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0009000000-d2c945077b93a0423349Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00e9-4091000000-4a8bdcd3ca72bcad379cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-06ad1e364d70213564e8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0039000000-17396abffdd86c9873e9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05e9-1291000000-4d8a424af3692977794bSpectrum
MSMass Spectrum (Electron Ionization)splash10-052b-4490000000-6bbd0d2c0c8fe332c636Spectrum
Toxicity Profile
Route of ExposureOral, rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single doser.
Mechanism of ToxicityAmoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
MetabolismAmoxapine 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsToxic 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.
TreatmentTreatment of amoxapine overdosage should be symptomatic and supportive, but with special attention to prevention or control of seizures. If the patient is conscious, induced emesis followed by gastric lavage with appropriate precautions to prevent pulmonary aspiration should be accomplished as soon as possible. Following lavage, activated charcoal may be administered to reduce absorption, and repeated administrations may facilitate drug elimination. An adequate airway should be established in comatose patients and assisted ventilation instituted if necessary. Seizures may respond to standard anticonvulsant therapy such as intravenous diazepam and/or phenytoin. The value of physostigmine appears less certain. Status epilepticus, should it develop, requires vigorous treatment. (2)
Concentrations
Not Available
DrugBank IDDB00543
HMDB IDHMDB0014683
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkAmoxapine
Chemspider ID2085
ChEBI ID2675
PubChem Compound ID2170
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
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

MSDSNot Available
General ReferencesNot Available