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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2022-03-07 02:51:39 UTC
HMDB IDHMDB0014552
Secondary Accession Numbers
  • HMDB14552
Metabolite Identification
Common NameLoxapine
DescriptionLoxapine, also known as cloxazepine or loxapinum, 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. Several researchers have argued that loxapine may behave as an atypical antipsychotic. Loxapine is a drug which is used for the management of the manifestations of psychotic disorders such as schizophrenia. Loxapine is a very strong basic compound (based on its pKa). Loxapine is a potentially toxic compound. Loxapine (several trade names worldwide) is a typical antipsychotic medication used primarily in the treatment of schizophrenia. The US Food and Drug Administration (FDA) has approved loxapine inhalation powder for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. A brief review of loxapine found no conclusive evidence that it was particularly effective in patients with paranoid schizophrenia. At lower dosages its propensity for causing extrapyramidal side effects appears to be similar to that of atypical antipsychoticsBlurred visionUrinary retentionSomnolence (which appears to be moderate in severity compared to other antipsychotic drugs)DyspnoeaNasal congestionRare side effects includeParalytic ileusAgranulocytosisLeukopeniaThrombocytopeniaHepatocellular liver damageNeuroleptic malignant syndromeSeizureTardive dyskinesiaStrokeTransient ischaemic attackDeathThe data in the table to the right was obtained from the PDSP Ki database and they are for binding towards human cloned proteins (receptor and transporter) unless otherwise specified. Loxapine may be metabolized by N-demethylation to amoxapine, a tricyclic antidepressant. This drug is unrelated to the habit-forming benzodiazepines, and misuse is rare. Note: Percentages given after possible adverse effects refer to the incidence of said adverse effects, according to DrugPoint.
Structure
Data?1582753192
Synonyms
ValueSource
2-Chloro-11-(4-methyl-1-piperazinyl)dibenz[b,F][1,4]oxazepineChEBI
CloxazepineChEBI
LoxapinaChEBI
LoxapinumChEBI
OxilapineChEBI
AdasuveKegg
Loxapine hydrochlorideHMDB
Loxapine succinateHMDB
Loxipine maleateHMDB
Loxapine monohydrochlorideHMDB
LoxapinsuccinateHMDB
Succinate, loxapineHMDB
Hydrochloride, loxapineHMDB
Loxipine succinateHMDB
LoxitaneHMDB
2-Chloro-11-(4-methyl-1-piperazinyl)-dibenz(b,F)(1,4)oxazepineHMDB
Maleate, loxipineHMDB
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
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
  • 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
Physiological effectNot Available
Disposition
ProcessNot Available
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point109 - 110 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.1 g/LNot Available
LogP3.6Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM175.730932474
[M+H]+Not Available176.383http://allccs.zhulab.cn/database/detail?ID=AllCCS00001100
Predicted Molecular 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
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]+171.61730932474
DeepCCS[M-H]-169.25930932474
DeepCCS[M-2H]-202.14430932474
DeepCCS[M+Na]+177.7130932474
AllCCS[M+H]+175.132859911
AllCCS[M+H-H2O]+171.832859911
AllCCS[M+NH4]+178.032859911
AllCCS[M+Na]+178.932859911
AllCCS[M-H]-178.032859911
AllCCS[M+Na-2H]-177.332859911
AllCCS[M+HCOO]-176.632859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
LoxapineCN1CCN(CC1)C1=NC2=CC=CC=C2OC2=C1C=C(Cl)C=C23867.7Standard polar33892256
LoxapineCN1CCN(CC1)C1=NC2=CC=CC=C2OC2=C1C=C(Cl)C=C22630.0Standard non polar33892256
LoxapineCN1CCN(CC1)C1=NC2=CC=CC=C2OC2=C1C=C(Cl)C=C22622.6Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Loxapine GC-MS (Non-derivatized) - 70eV, Positivesplash10-06r5-8094000000-3f11548f145e2cd0d2a52017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Loxapine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a4l-7590000000-118f30ca0699bf2b3d2e2014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Loxapine LC-ESI-qTof , Positive-QTOFsplash10-00ai-0149000000-d463f8ddf4248264d1322017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Loxapine LC-ESI-qTof , Positive-QTOFsplash10-01r6-0930000000-4798aec046d747300d802017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Loxapine , positive-QTOFsplash10-00ai-0149000000-d463f8ddf4248264d1322017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Loxapine , positive-QTOFsplash10-01r6-0930000000-4798aec046d747300d802017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Loxapine 35V, Positive-QTOFsplash10-00di-0092000000-d36334adec23dfc827b72021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 10V, Positive-QTOFsplash10-004i-0009000000-13c7c5980fa375485ea62016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 20V, Positive-QTOFsplash10-004i-0029000000-ee11b761132aadb447f82016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 40V, Positive-QTOFsplash10-0596-9250000000-cdb8e78cf5fd1fd059b92016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 10V, Negative-QTOFsplash10-004i-0009000000-71d4c9395b89ad9fc22a2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 20V, Negative-QTOFsplash10-004i-0039000000-ca6576c997e0e1af0ab22016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 40V, Negative-QTOFsplash10-006y-3491000000-40caba03e0caacbf4b762016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 10V, Positive-QTOFsplash10-004i-0009000000-1f57d14978e5410155ca2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 20V, Positive-QTOFsplash10-004i-0019000000-171a44896a8b8aa671512021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 40V, Positive-QTOFsplash10-00di-0090000000-8f9b474f4d539ce49d692021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 10V, Negative-QTOFsplash10-004i-0009000000-f859e2aff8bfc6f7a27b2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 20V, Negative-QTOFsplash10-004i-0039000000-568c941d47f67e7c6c412021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Loxapine 40V, Negative-QTOFsplash10-001i-5091000000-1f13f155778e72cff1182021-09-23Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00408 details
UrineExpected but not QuantifiedNot QuantifiedNot 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
FooDB 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
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 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 ]