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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2019-01-11 19:33:48 UTC
HMDB IDHMDB0014552
Secondary Accession Numbers
  • HMDB14552
Metabolite Identification
Common NameLoxapine
DescriptionLoxapine is only found in individuals that have used or taken this drug. It is an antipsychotic agent used in schizophrenia. [PubChem]Loxapine is a dopamine antagonist, and also a serotonin 5-HT2 blocker. The exact mode of action of Loxapine has not been established, however changes in the level of excitability of subcortical inhibitory areas have been observed in several animal species in association with such manifestations of tranquilization as calming effects and suppression of aggressive behavior.
Structure
Data?1547235228
Synonyms
ValueSource
2-chloro-11-(4-Methyl-1-piperazinyl)dibenz[b,F][1,4]oxazepineChEBI
CloxazepineChEBI
LoxapinaChEBI
LoxapinumChEBI
OxilapineChEBI
Loxapine hydrochlorideMeSH
Loxapine succinateMeSH
Loxipine maleateMeSH
Loxapine monohydrochlorideMeSH
LoxapinsuccinateMeSH
Succinate, loxapineMeSH
Hydrochloride, loxapineMeSH
Loxipine succinateMeSH
LoxitaneMeSH
2-chloro-11-(4-Methyl-1-piperazinyl)-dibenz(b,F)(1,4)oxazepineMeSH
Maleate, loxipineMeSH
Chemical FormulaC18H18ClN3O
Average Molecular Weight327.808
Monoisotopic Molecular Weight327.11383992
IUPAC Name13-chloro-10-(4-methylpiperazin-1-yl)-2-oxa-9-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3,5,7,9,12,14-heptaene
Traditional Nameloxapine
CAS Registry Number1977-10-2
SMILES
CN1CCN(CC1)C1=NC2=CC=CC=C2OC2=C1C=C(Cl)C=C2
InChI Identifier
InChI=1S/C18H18ClN3O/c1-21-8-10-22(11-9-21)18-14-12-13(19)6-7-16(14)23-17-5-3-2-4-15(17)20-18/h2-7,12H,8-11H2,1H3
InChI KeyXJGVXQDUIWGIRW-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzoxazepines
Sub ClassDibenzoxazepines
Direct ParentDibenzoxazepines
Alternative Parents
Substituents
  • Dibenzoxazepine
  • Diaryl ether
  • N-methylpiperazine
  • N-alkylpiperazine
  • Aryl chloride
  • Aryl halide
  • 1,4-diazinane
  • Piperazine
  • Benzenoid
  • Imidolactam
  • Tertiary amine
  • Tertiary aliphatic amine
  • Oxacycle
  • Azacycle
  • Carboxylic acid amidine
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Ether
  • Amidine
  • Amine
  • Organic oxygen compound
  • Organohalogen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point109 - 110 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.1 g/LNot Available
LogP3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.1 g/LALOGPS
logP3.18ALOGPS
logP3.46ChemAxon
logS-3.5ALOGPS
pKa (Strongest Basic)7.18ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area28.07 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity95.11 m³·mol⁻¹ChemAxon
Polarizability34.99 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06r5-8094000000-3f11548f145e2cd0d2a5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00ai-0149000000-d463f8ddf4248264d132View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-01r6-0930000000-4798aec046d747300d80View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00ai-0149000000-d463f8ddf4248264d132View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-01r6-0930000000-4798aec046d747300d80View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0009000000-13c7c5980fa375485ea6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0029000000-ee11b761132aadb447f8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0596-9250000000-cdb8e78cf5fd1fd059b9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0009000000-71d4c9395b89ad9fc22aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0039000000-ca6576c997e0e1af0ab2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-006y-3491000000-40caba03e0caacbf4b76View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a4l-7590000000-118f30ca0699bf2b3d2eView in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00408 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00408 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 IDDB00408
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3827
KEGG Compound IDC07104
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLoxapine
METLIN IDNot Available
PubChem Compound3964
PDB IDNot Available
ChEBI ID50841
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Cheung SW, Tang SW, Remington G: Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography. J Chromatogr. 1991 Mar 8;564(1):213-21. [PubMed:1860915 ]
  2. Glazer WM: Does loxapine have "atypical" properties? Clinical evidence. J Clin Psychiatry. 1999;60 Suppl 10:42-6. [PubMed:10340686 ]

Enzymes

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. Lee T, Tang SW: Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry Res. 1984 Aug;12(4):277-85. [PubMed:6239298 ]
  2. Hjerde E, Dahl SG, Sylte I: Atypical and typical antipsychotic drug interactions with the dopamine D2 receptor. Eur J Med Chem. 2005 Feb;40(2):185-94. [PubMed:15694653 ]
  3. Kalkman HO, Neumann V, Nozulak J, Tricklebank MD: Cataleptogenic effect of subtype selective 5-HT receptor antagonists in the rat. Eur J Pharmacol. 1998 Feb 19;343(2-3):201-7. [PubMed:9570468 ]
  4. Froimowitz M, Cody V: Biologically active conformers of phenothiazines and thioxanthenes. Further evidence for a ligand model of dopamine D2 receptor antagonists. J Med Chem. 1993 Jul 23;36(15):2219-27. [PubMed:8101879 ]
  5. Froimowitz M, Cody V: The incorporation of butyrophenones and related compounds into a pharmacophore for dopamine D2 antagonists. Drug Des Discov. 1997 Aug;15(2):63-81. [PubMed:9342550 ]
  6. Lang AE, Sandor P, Duff J: Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis. Clin Neuropharmacol. 1995 Feb;18(1):39-45. [PubMed:8665533 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
References
  1. Li Z, Ichikawa J, Meltzer HY: A comparison of the effects of loxapine with ziprasidone and thioridazine on the release of dopamine and acetylcholine in the prefrontal cortex and nucleus accumbens. Psychopharmacology (Berl). 2003 May;167(3):315-23. Epub 2003 Mar 28. [PubMed:12664192 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular weight:
51820.7
References
  1. Herrick-Davis K, Grinde E, Teitler M: Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther. 2000 Oct;295(1):226-32. [PubMed:10991983 ]
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]