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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2022-03-07 02:51:42 UTC
HMDB IDHMDB0014683
Secondary Accession Numbers
  • HMDB14683
Metabolite Identification
Common NameAmoxapine
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.
Structure
Data?1582753208
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 Weight313.781
Monoisotopic Molecular Weight313.098189856
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
CAS Registry Number14028-44-5
SMILES
ClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C1
InChI Identifier
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
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
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point175.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.17 g/LNot Available
LogP3.4Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM170.230932474
[M+H]+Not Available171.19http://allccs.zhulab.cn/database/detail?ID=AllCCS00001109
Predicted Molecular 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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+173.39930932474
DeepCCS[M-H]-171.04130932474
DeepCCS[M-2H]-203.92730932474
DeepCCS[M+Na]+179.49230932474
AllCCS[M+H]+171.332859911
AllCCS[M+H-H2O]+167.932859911
AllCCS[M+NH4]+174.432859911
AllCCS[M+Na]+175.232859911
AllCCS[M-H]-173.032859911
AllCCS[M+Na-2H]-172.232859911
AllCCS[M+HCOO]-171.632859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
AmoxapineClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C13987.0Standard polar33892256
AmoxapineClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C12671.8Standard non polar33892256
AmoxapineClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C12667.4Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Amoxapine,1TMS,isomer #1C[Si](C)(C)N1CCN(C2=NC3=CC=CC=C3OC3=CC=C(Cl)C=C23)CC12899.7Semi standard non polar33892256
Amoxapine,1TMS,isomer #1C[Si](C)(C)N1CCN(C2=NC3=CC=CC=C3OC3=CC=C(Cl)C=C23)CC12748.2Standard non polar33892256
Amoxapine,1TMS,isomer #1C[Si](C)(C)N1CCN(C2=NC3=CC=CC=C3OC3=CC=C(Cl)C=C23)CC14154.0Standard polar33892256
Amoxapine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN(C2=NC3=CC=CC=C3OC3=CC=C(Cl)C=C23)CC13119.5Semi standard non polar33892256
Amoxapine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN(C2=NC3=CC=CC=C3OC3=CC=C(Cl)C=C23)CC12939.5Standard non polar33892256
Amoxapine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN(C2=NC3=CC=CC=C3OC3=CC=C(Cl)C=C23)CC14334.2Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Amoxapine GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-6190000000-1acb98762576326ae75b2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Amoxapine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Amoxapine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-052b-4490000000-6bbd0d2c0c8fe332c6362014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine LC-ESI-qTof , Positive-QTOFsplash10-00dl-2690000000-0e598ca107ca857b8f062017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine , positive-QTOFsplash10-044i-0169000000-d1665f2e6d27a9efaa392017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine , positive-QTOFsplash10-002f-0940000000-9bf5c13f1f2b9b04f4652017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine , positive-QTOFsplash10-00dl-2690000000-0e598ca107ca857b8f062017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 75V, Positive-QTOFsplash10-006x-2950000000-2fb725746001d0be41d12021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 90V, Positive-QTOFsplash10-0006-0910000000-7df25fea8ffb96c66d502021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 30V, Positive-QTOFsplash10-03k9-1059000000-99ec364d324293ba91912021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 15V, Positive-QTOFsplash10-03di-0009000000-fb09780a1d33ba8eb3c82021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 45V, Positive-QTOFsplash10-00di-2090000000-046bbbcb38472a6b5a4c2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 60V, Positive-QTOFsplash10-00di-2290000000-47774f87a43619d76d342021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Amoxapine 60V, Positive-QTOFsplash10-00di-2290000000-53b12cd961449d9ea6342021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 10V, Positive-QTOFsplash10-03di-0009000000-873be01dd22731e1f7a72016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 20V, Positive-QTOFsplash10-03di-0049000000-3989b74ad41770f20ee02016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 40V, Positive-QTOFsplash10-01r6-9440000000-54259557a6e11d912eb72016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 10V, Negative-QTOFsplash10-03di-0019000000-eaaa73a51b5bbc0bf28b2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 20V, Negative-QTOFsplash10-03di-0049000000-be3ce6855a4cc094b8fc2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 40V, Negative-QTOFsplash10-0006-9250000000-d2f001cf68189e0c19d42016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 10V, Negative-QTOFsplash10-03di-0009000000-c66d97d82d39ee90b5852021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 20V, Negative-QTOFsplash10-03di-0009000000-d2c945077b93a04233492021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 40V, Negative-QTOFsplash10-00e9-4091000000-4a8bdcd3ca72bcad379c2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 10V, Positive-QTOFsplash10-03di-0009000000-06ad1e364d70213564e82021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 20V, Positive-QTOFsplash10-03di-0039000000-17396abffdd86c9873e92021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Amoxapine 40V, Positive-QTOFsplash10-05e9-1291000000-4d8a424af3692977794b2021-09-24Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00543 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00543 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00543
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2085
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAmoxapine
METLIN IDNot Available
PubChem Compound2170
PDB IDNot Available
ChEBI ID2675
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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) proteins
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular weight:
51486.0
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 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular weight:
51801.4
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular weight:
49292.8
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 action of G proteins. Primary transducing effect is Pi turnover
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular weight:
51420.4
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 ]

Transporters

General function:
Involved in neurotransmitter: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
Molecular weight:
69331.42
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 ]
General function:
Involved in neurotransmitter: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 the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular weight:
70324.165
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 ]