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Details

Stereochemistry ACHIRAL
Molecular Formula C18H18ClN3O
Molecular Weight 327.808
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOXAPINE

SMILES

CN1CCN(CC1)C2=NC3=CC=CC=C3OC4=CC=C(Cl)C=C24

InChI

InChIKey=XJGVXQDUIWGIRW-UHFFFAOYSA-N
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

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

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
2849
 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
2849
 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
2849
 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
2849
 9.0 nM [Ki]
Histamine H1 receptor
316
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2849
 15.0 nM [Ki]
Muscarinic acetylcholine receptor M1
168
Target ID: P11229
Gene ID: 1128.0
Gene Symbol: CHRM1
Target Organism: Homo sapiens (Human)
Antagonist
2849
 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
2849
 250.0 nM [Ki]
5-hydroxytryptamine receptor 2A
73
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Antagonist
2849
 2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
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
8583
Adasuve

Approved Use

Schizophrenia

Launch Date

2012
Primary
Approved
8583
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
1946

inhibitor
2252
substrate
1193

inhibitor
2438
substrate
1388

inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1741

CYP1A1
132

CYP1A2
2153

CYP2A6
879

CYP2B6
926

CYP2C8
1057

CYP2C19
2057

CYP2E1
1060
CYP1A2
1197

FMO
34

P-gp
2052

CYP3A4/5
91

CYP2C8
810

CYP2C19
1119
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
272
 no
CYP1A2
2333
 no
CYP2A6
911
 no
CYP2B6
1160
 no
CYP2C19
2141
 no
CYP2C8
1117
 no
CYP2C9
2497
 no
CYP2D6
2546
 no
CYP2E1
1146
 no
CYP3A4
2633
 no
P-gp
1932
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
1119
 minor
P-gp
2052
 no
no (co-administration study)
Comment: ketoconazole did not affect loxapine transport
Page: 20.0
CYP1A2
1197
 yes
CYP2C8
810
 yes
CYP2C9
1193
 yes
CYP2D6
1388
 yes
CYP3A4
1946
 yes
CYP3A4/5
91
 yes
FMO
34
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
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
In vitro identification of the human cytochrome p450 enzymes involved in the oxidative metabolism of loxapine.
2011-10
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010-12
Validation of HPLC-MS/MS methods for analysis of loxapine, amoxapine, 7-OH-loxapine, 8-OH-loxapine and loxapine N-oxide in human plasma.
2010-12
Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients.
2010-11-10
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.
2010-09-17
In vitro aerosol deposition in the oropharyngeal region for Staccato loxapine.
2010-08
Pharmacological interventions for borderline personality disorder.
2010-06-16
Chem2Bio2RDF: a semantic framework for linking and data mining chemogenomic and systems chemical biology data.
2010-05-17
4-Nitro-2-phenoxy-aniline.
2010-05-08
Identifying unexpected therapeutic targets via chemical-protein interactome.
2010-03-08
[Catatonia in a 14 year-old girl: treatment with clorazepam and carbamazepine, a 10-year follow-up].
2010-02
Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers.
2010-02
Current perspectives in the treatment of resistant schizophrenia.
2010-01-06
An overview of Indian research in schizophrenia.
2010-01
Simultaneous HPLC determination of 14 tricyclic antidepressants and metabolites in human plasma.
2010-01
Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation.
2010
The association between class of antipsychotic and rates of hospitalization: results of a retrospective analysis of data from the 2005 Medicare current beneficiary survey.
2009-12
Psychotic woman with painful abdominal distension. Life-threatening psychotropic drug-induced gastrointestinal hypomotility.
2009-11
Bacitracin-sensitive aminopeptidase(s) degradation of methionine(5)-enkephalin by human brain putamen and hippocampus preparations: inhibition by phenothiazine drugs.
2009-10-03
Use and safety of antipsychotic drugs during pregnancy.
2009-05
Neuroanatomical, neurochemical, and neurodevelopmental basis of obsessive-compulsive symptoms in schizophrenia.
2009-01
Safety and efficacy of antipsychotic drugs for the behavioral and psychological symptoms of dementia.
2009-01
Spectroscopic and electrochemical analysis of psychotropic drugs.
2009-01
Finding my faith.
2009-01
Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N-desmethyl clozapine (norclozapine) in human serum.
2009
The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913).
2008-12-22
Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients.
2008-10
HPLC analysis of the antidepressant trazodone and its main metabolite m-CPP in human plasma.
2008-08-05
Analysis of the recent antipsychotic aripiprazole in human plasma by capillary electrophoresis and high-performance liquid chromatography with diode array detection.
2008-04-07
Incorporating clinical guidelines through clinician decision-making.
2008-02-29
Modifications of antiepileptic drugs for improved tolerability and efficacy.
2008-02-14
Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia.
2008-01
Loxapine for schizophrenia.
2007-10-17
Clozapine: Current perspective.
2007-10
Pharmacological causes of hyperprolactinemia.
2007-10
Determination of clozapine and its metabolite, norclozapine in various biological matrices using high-performance liquid chromatography.
2007-10
HPLC analysis of the novel antidepressant duloxetine in human plasma after an original solid-phase extraction procedure.
2007-09-01
Correlations between weight changes and lipid profile changes in schizophrenic patients after antipsychotics therapy.
2007-05-05
Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma.
2007-05
Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.
2007-04
Simultaneous determination of methadone, buprenorphine and norbuprenorphine in biological fluids for therapeutic drug monitoring purposes.
2007-03-01
Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients.
2007-02-27
Effect of loxapine on electrical brain activity, intracranial pressure, and middle cerebral artery flow velocity in traumatic brain-injured patients.
2007
Lack of enhanced effect of antipsychotics combined with fluvoxamine on acetylcholine release in rat prefrontal cortex.
2006-12
[Therapeutics approach of adult patients with acute and chronic psychotic states: REALITE survey].
2006-11-14
Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients.
2006-11
Loxapine treatment in an autistic child with aggressive behavior: therapeutic challenges.
2006-10
Treatment-refractory schizophrenia.
2004-03
Treatment of the special patient with schizophrenia.
2001-06
Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography.
1991-03-08
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 Mon Mar 31 18:47:27 GMT 2025
Edited
by admin
on Mon Mar 31 18:47:27 GMT 2025
Record UNII
LER583670J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADASUVE
Preferred Name English
LOXAPINE
HSDB   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
SUM-3170
Code English
SUM 3170
Code English
CL 62,362
Code English
2-CHLORO-11-(4-METHYL-1-PIPERAZINYL)DIBENZ(B,F)(1,4)OXAZEPINE
Systematic Name English
loxapine [INN]
Common Name English
LOXAPINE [USAN]
Common Name English
DIBENZ(B,F)(1,4)OXAZEPINE, 2-CHLORO-11-(4-METHYL-1-PIPERAZINYL)-
Systematic Name English
CL-62362
Code English
LOXAPINE [MI]
Common Name English
LOXAPINE [VANDF]
Common Name English
Loxapine [WHO-DD]
Common Name English
LOXAPINE [ORANGE BOOK]
Common Name English
LOXAPINE [HSDB]
Common Name English
LOXAPINE [MART.]
Common Name English
Classification Tree Code System Code
LIVERTOX NBK548875
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
NCI_THESAURUS C29710
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: SCHIZOPHRENIA)
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
WHO-VATC QN05AH01
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
WHO-ATC N05AH01
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: BIPOLAR DISORDER)
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
Code System Code Type Description
WIKIPEDIA
LOXAPINE
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
DAILYMED
LER583670J
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
CAS
1977-10-2
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
RXCUI
6475
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY RxNorm
PUBCHEM
3964
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
ECHA (EC/EINECS)
217-835-3
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
HSDB
3111
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
IUPHAR
205
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PRIMARY
DRUG BANK
DB00408
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
DRUG CENTRAL
1613
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
EPA CompTox
DTXSID7023229
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
FDA UNII
LER583670J
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
INN
2610
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
NCI_THESAURUS
C61816
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
MERCK INDEX
m6915
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY Merck Index
MESH
D008152
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
ChEMBL
CHEMBL831
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
SMS_ID
100000092266
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PRIMARY
CHEBI
50841
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
LACTMED
Loxapine
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
EVMPD
SUB08607MIG
Created by admin on Mon Mar 31 18:47:27 GMT 2025 , Edited by admin on Mon Mar 31 18:47:27 GMT 2025
PRIMARY
Related Record Type Details
Structure of Loxapine Succinate
SALT/SOLVATE -> PARENT
5-HYDROXYTRYPTAMINE RECEPTOR 2A
TARGET -> INHIBITOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Structure of LOXAPINE HYDROCHLORIDE
SALT/SOLVATE -> PARENT
ALDEHYDE OXIDASE
METABOLIC ENZYME -> INHIBITOR
IC50
Related Record Type Details
Structure of 7-HYDROXYAMOXAPINE
METABOLITE -> PARENT
MINOR
URINE
Structure of 7-HYDROXYLOXAPINE
METABOLITE -> PARENT
Structure of 8-HYDROXYLOXAPINE
METABOLITE -> PARENT
Structure of 7-HYDROXYLOXAPINE
METABOLITE -> PARENT
MINOR
PLASMA; URINE
Structure of Amoxapine
METABOLITE -> PARENT
Structure of Loxapine N-oxide
METABOLITE -> PARENT
MINOR
PLASMA
Structure of 7-HYDROXYLOXAPINE
METABOLITE -> PARENT
Structure of 8-HYDROXYAMOXAPINE
METABOLITE -> PARENT
PLASMA; URINE
Structure of 8-HYDROXYLOXAPINE
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA; URINE
Structure of Loxapine N-oxide
METABOLITE -> PARENT
Mediator: flavanoid monoamine oxidases
Related Record Type Details
Structure of LOXAPINE
ACTIVE MOIETY
NIH
NCATS
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HHS VULNERABILITY DISCLOSURE
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