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Details

Stereochemistry ACHIRAL
Molecular Formula C18H18ClN3O.C4H6O4
Molecular Weight 445.896
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOXAPINE SUCCINATE

SMILES

OC(=O)CCC(O)=O.CN1CCN(CC1)C2=NC3=C(OC4=C2C=C(Cl)C=C4)C=CC=C3

InChI

InChIKey=YQZBAXDVDZTKEQ-UHFFFAOYSA-N
InChI=1S/C18H18ClN3O.C4H6O4/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;5-3(6)1-2-4(7)8/h2-7,12H,8-11H2,1H3;1-2H2,(H,5,6)(H,7,8)

HIDE SMILES / InChI
Molecular Formula C18H18ClN3O
Molecular Weight 327.808
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C4H6O4
Molecular Weight 118.088
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25859275

Loxapine is a dibenzoxazepine tricyclic antipsychotic agent, available for oral and inhalatory administration, classified as a typical antipsychotic. Loxapine acts as an antagonist at central serotonin and dopamine receptors. Adasuve (loxapine inhalation powder) is a prescription medicine that is used to treat acute agitation in adults with schizophrenia or bipolar I disorder.

CNS Activity

Originator

Approval Year

1975
63
Targets

Targets

Primary TargetPharmacologyConditionPotency
D(1A) dopamine receptor
18
Target ID: P21728
Gene ID: 1812.0
Gene Symbol: DRD1
Target Organism: Homo sapiens (Human)
Antagonist
2778
 18.0 nM [Ki]
D(2) dopamine receptor
58
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
Antagonist
2778
 10.0 nM [Ki]
D(3) dopamine receptor
16
Target ID: P35462
Gene ID: 1814.0
Gene Symbol: DRD3
Target Organism: Homo sapiens (Human)
Antagonist
2778
 21.0 nM [Ki]
D(4) dopamine receptor
3
Target ID: P21917
Gene ID: 1815.0
Gene Symbol: DRD4
Target Organism: Homo sapiens (Human)
Antagonist
2778
 9.0 nM [Ki]
Histamine H1 receptor
315
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2778
 15.0 nM [Ki]
Muscarinic acetylcholine receptor M1
169
Target ID: P11229
Gene ID: 1128.0
Gene Symbol: CHRM1
Target Organism: Homo sapiens (Human)
Antagonist
2778
 117.0 nM [Ki]
Alpha-2A adrenergic receptor
26
Target ID: P08913
Gene ID: 150.0
Gene Symbol: ADRA2A
Target Organism: Homo sapiens (Human)
Antagonist
2778
 250.0 nM [Ki]
5-hydroxytryptamine receptor 2A
69
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Antagonist
2778
 2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
LOXITANE

Approved Use

Loxapine Capsules, USP are indicated for the treatment of schizophrenia. The efficacy of loxapine in schizophrenia was established in clinical studies which enrolled newly hospitalized and chronically hospitalized acutely ill schizophrenic patients as subjects.

Launch Date

1975
Primary
Approved
8429
Adasuve

Approved Use

Schizophrenia

Launch Date

2012
Primary
Approved
8429
Adasuve

Approved Use

Bipolar I disorder

Launch Date

2012
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
257 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022549s000lbl.pdf
10 mg single, respiratory
dose: 10 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
LOXAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
188 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022549s000lbl.pdf
10 mg single, respiratory
dose: 10 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
LOXAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.61 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022549s000lbl.pdf
10 mg single, respiratory
dose: 10 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
LOXAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3.4%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022549s000lbl.pdf
10 mg single, respiratory
dose: 10 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
LOXAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
substrate
1037

inhibitor
1767
substrate
1217

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461

CYP1A1
110

CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP2E1
882
CYP1A2
1054

FMO
35

P-gp
1537

CYP3A4/5
85

CYP2C8
693

CYP2C19
991
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
218
 no
CYP1A2
1692
 no
CYP2A6
739
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A4
1925
 no
P-gp
1650
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
991
 minor
P-gp
1537
 no
no (co-administration study)
Comment: ketoconazole did not affect loxapine transport
Page: 20.0
CYP1A2
1054
 yes
CYP2C8
693
 yes
CYP2C9
1037
 yes
CYP2D6
1217
 yes
CYP3A4
1737
 yes
CYP3A4/5
85
 yes
FMO
35
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:50841
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50841
MolPort
MolPort-002-885-838
https://www.molport.com/shop/molecule-link/MolPort-002-885-838
ZINC
ZINC000019796158
http://zinc15.docking.org/substances/ZINC000019796158
PubMed

PubMed

TitleDatePubMed
Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography.
1991 Mar 8
Treatment of the special patient with schizophrenia.
2001 Jun
Treatment-refractory schizophrenia.
2004 Mar
Atypical and typical antipsychotic drug interactions with the dopamine D2 receptor.
2005 Feb
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
NMS after clozapine initiation.
2005 Nov
Contrasting loxapine to its isomer isoloxapine--the critical role of in vivo D2 blockade in determining atypicality.
2005 Sep 15
Increasing psychosis in a patient switched from clozaril to generic clozapine.
2006 Apr
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia.
2006 Feb 21
[Efficacy and adverse reactions of antipsychotics for neuropsychiatric symptoms in dementia: a systematic review].
2006 Jul 15
Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up.
2006 Jun
[Clinical and socio-demographic profile of patients with schizophrenia according to the antipsychotic treatment prescribed].
2006 May-Jun
Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients.
2006 Nov
Synthesis, characterization, antimicrobial and single crystal X-ray crystallographic studies of some new sulfonyl, 4-chloro phenoxy benzene and dibenzoazepine substituted benzamides.
2006 Nov
Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review.
2006 Sep
Simultaneous determination of the antipsychotic drugs levomepromazine and clozapine and their main metabolites in human plasma by a HPLC-UV method with solid-phase extraction.
2007 Feb 1
Simultaneous determination of methadone, buprenorphine and norbuprenorphine in biological fluids for therapeutic drug monitoring purposes.
2007 Mar 1
Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma.
2007 May
Clozapine: Current perspective.
2007 Oct
Pharmacological causes of hyperprolactinemia.
2007 Oct
Determination of clozapine and its metabolite, norclozapine in various biological matrices using high-performance liquid chromatography.
2007 Oct
HPLC analysis of the antidepressant trazodone and its main metabolite m-CPP in human plasma.
2008 Aug 5
Modifications of antiepileptic drugs for improved tolerability and efficacy.
2008 Feb 14
Incorporating clinical guidelines through clinician decision-making.
2008 Feb 29
Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients.
2008 Oct
Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N-desmethyl clozapine (norclozapine) in human serum.
2009
The association between class of antipsychotic and rates of hospitalization: results of a retrospective analysis of data from the 2005 Medicare current beneficiary survey.
2009 Dec
Neuroanatomical, neurochemical, and neurodevelopmental basis of obsessive-compulsive symptoms in schizophrenia.
2009 Jan
Safety and efficacy of antipsychotic drugs for the behavioral and psychological symptoms of dementia.
2009 Jan
Spectroscopic and electrochemical analysis of psychotropic drugs.
2009 Jan
Finding my faith.
2009 Jan
Use and safety of antipsychotic drugs during pregnancy.
2009 May
Psychotic woman with painful abdominal distension. Life-threatening psychotropic drug-induced gastrointestinal hypomotility.
2009 Nov
Bacitracin-sensitive aminopeptidase(s) degradation of methionine(5)-enkephalin by human brain putamen and hippocampus preparations: inhibition by phenothiazine drugs.
2009 Nov-Dec
Current perspectives in the treatment of resistant schizophrenia.
2009 Oct-Dec
Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation.
2010
In vitro aerosol deposition in the oropharyngeal region for Staccato loxapine.
2010 Aug
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Validation of HPLC-MS/MS methods for analysis of loxapine, amoxapine, 7-OH-loxapine, 8-OH-loxapine and loxapine N-oxide in human plasma.
2010 Dec
[Catatonia in a 14 year-old girl: treatment with clorazepam and carbamazepine, a 10-year follow-up].
2010 Feb
Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers.
2010 Feb
An overview of Indian research in schizophrenia.
2010 Jan
Simultaneous HPLC determination of 14 tricyclic antidepressants and metabolites in human plasma.
2010 Jan
Pharmacological interventions for borderline personality disorder.
2010 Jun 16
Identifying unexpected therapeutic targets via chemical-protein interactome.
2010 Mar 8
Chem2Bio2RDF: a semantic framework for linking and data mining chemogenomic and systems chemical biology data.
2010 May 17
4-Nitro-2-phenoxy-aniline.
2010 May 8
Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients.
2010 Nov 10
A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting.
2010 Sep 17
In vitro identification of the human cytochrome p450 enzymes involved in the oxidative metabolism of loxapine.
2011 Oct
Patents

Patents

8288372
3
US20040102434
3
US20070042014
3
WO/1993/014759A1
3
WO/2004/047844A1
3

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Loxitane (loxapine) capsules are prescribed for schizophrenia in dosage 10 mg twice daily (initial dose, orally) http://www.rxlist.com/loxitane-drug/indications-dosage.htm
Adasuve (loxapine inhalation powder), 10 mg by oral inhalation
Route of Administration: Respiratory
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:35:18 GMT 2023
Edited
by admin
on Fri Dec 15 15:35:18 GMT 2023
Record UNII
X59SG0MRYU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOXAPINE SUCCINATE
MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
LOXAPINE SUCCINATE [USP-RS]
Common Name English
Loxapine succinate [WHO-DD]
Common Name English
LOXAPINE SUCCINATE [USP MONOGRAPH]
Common Name English
LOXAPINE SUCCINATE [ORANGE BOOK]
Common Name English
LOXAPINE SUCCINATE [MART.]
Common Name English
NSC-759578
Code English
CL 71563
Code English
LOXAPINE SUCCINATE [VANDF]
Common Name English
LOXAPINE SUCCINATE [USAN]
Common Name English
CL-71563
Code English
LOXAPINE SUCCINATE [MI]
Common Name English
LOXITANE
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C29710
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
Code System Code Type Description
MERCK INDEX
m6915
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY Merck Index
RS_ITEM_NUM
1370702
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
ECHA (EC/EINECS)
248-682-0
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
EPA CompTox
DTXSID3045227
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
EVMPD
SUB02977MIG
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
NSC
759578
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
SMS_ID
100000091839
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
NCI_THESAURUS
C47590
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
CAS
27833-64-3
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
DAILYMED
X59SG0MRYU
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
DRUG BANK
DBSALT001194
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
PUBCHEM
71399
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
ChEMBL
CHEMBL831
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
RXCUI
6476
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY RxNorm
FDA UNII
X59SG0MRYU
Created by admin on Fri Dec 15 15:35:18 GMT 2023 , Edited by admin on Fri Dec 15 15:35:18 GMT 2023
PRIMARY
Related Record Type Details
Structure of LOXAPINE
PARENT -> SALT/SOLVATE
Structure of SUCCINIC ACID
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of 3-CHLORO-11-(4-METHYLPIPERAZIN-1-YL)DIBENZO(B,F)(1,4)OXAZEPINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of AMOXAPINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of 2-CHLORODIBENZO(B,F)-1,4-OXAZEPIN-11-ONE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of LOXAPINE
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