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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
Thioridazine for dementia.
2001
Clinically significant drug interactions with agents specific for migraine attacks.
2001
Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine.
2001 Dec 27
Re: Neuroleptic malignant syndrome associated with quetiapine.
2001 May
[Body weight changes and psychotropic drug treatment: neuroleptics].
2001 May-Jun
A new class of antiarrhythmic-defibrillatory agents.
2001 Nov 19
[Psychiatric manifestations of lupus erythematosus systemic and Sjogren's syndrome].
2001 Nov-Dec
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.
2001 Oct
Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation.
2002 Apr
[Self-poisoning with Datura stramonium. 3 case reports].
2002 Jan 19
Discriminative stimulus properties in rats of the novel antipsychotic quetiapine.
2002 Nov
Loxapine versus olanzapine in the treatment of delirium following traumatic brain injury.
2003
Human genetic variations in the 5HT2A receptor: a single nucleotide polymorphism identified with altered response to clozapine.
2003 Feb
Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake.
2003 May
Effects of some antidepressant drugs on tryptaminergic responses of the rat jejunum.
2003 Oct
Neuroleptic malignant syndrome: case report and discussion.
2003 Sep 2
Transient hyperproinsulinemia during treatment with clozapine and amisulpride.
2004 Jun
Treatment-refractory schizophrenia.
2004 Mar
An assessment of quality of sleep and the use of drugs with sedating properties in hospitalized adult patients.
2004 Mar 24
[Agranulocytosis induced by loxapine in an elderly patient: a case study].
2004 Sep-Oct
Minimally effective doses of conventional antipsychotic medications used to treat aggression, self-injurious and destructive behaviors in mentally retarded adults.
2005 Feb
Treatment of acute mania--from clinical trials to recommendations for clinical practice.
2005 Jan
Contrasting loxapine to its isomer isoloxapine--the critical role of in vivo D2 blockade in determining atypicality.
2005 Sep 15
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia.
2006 Feb 21
Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up.
2006 Jun
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
Loxapine for schizophrenia.
2007 Oct 17
HPLC analysis of the antidepressant trazodone and its main metabolite m-CPP in human plasma.
2008 Aug 5
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 Dec 22
Modifications of antiepileptic drugs for improved tolerability and efficacy.
2008 Feb 14
Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients.
2008 Oct
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
Use and safety of antipsychotic drugs during pregnancy.
2009 May
Current perspectives in the treatment of resistant schizophrenia.
2009 Oct-Dec
Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers.
2010 Feb
An overview of Indian research in schizophrenia.
2010 Jan
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
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
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 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
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
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
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