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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=C(OC4=C2C=C(Cl)C=C4)C=CC=C3

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
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
Thioridazine for dementia.
2001
Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine.
2001 Dec 27
Treatment of the special patient with schizophrenia.
2001 Jun
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.
2001 Oct
Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study.
2002
TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243].
2002 Oct 16
In vitro human plasma leucine(5)-enkephalin degradation is inhibited by a select number of drugs with the phenothiazine molecule in their chemical structure.
2003 Jan
Differential effects of atypical and typical antipsychotic drugs on N-methyl-D-aspartate- and electrically evoked responses in the pyramidal cells of the rat medial prefrontal cortex.
2003 May
Effects of some antidepressant drugs on tryptaminergic responses of the rat jejunum.
2003 Oct
Interspecies variability and drug interactions of loxapine metabolism in liver microsomes.
2003 Oct-Dec
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
Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures.
2005 Jan
Treatment of acute mania--from clinical trials to recommendations for clinical practice.
2005 Jan
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
Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients.
2006 Nov
Effect of loxapine on electrical brain activity, intracranial pressure, and middle cerebral artery flow velocity in traumatic brain-injured patients.
2007
Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.
2007 Apr
Correlations between weight changes and lipid profile changes in schizophrenic patients after antipsychotics therapy.
2007 Jan-Feb
Simultaneous determination of methadone, buprenorphine and norbuprenorphine in biological fluids for therapeutic drug monitoring purposes.
2007 Mar 1
Pharmacological causes of hyperprolactinemia.
2007 Oct
Determination of clozapine and its metabolite, norclozapine in various biological matrices using high-performance liquid chromatography.
2007 Oct
Loxapine for schizophrenia.
2007 Oct 17
HPLC analysis of the novel antidepressant duloxetine in human plasma after an original solid-phase extraction procedure.
2007 Sep 1
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
Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia.
2008 Jan
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
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
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
An overview of Indian research in schizophrenia.
2010 Jan
Identifying unexpected therapeutic targets via chemical-protein interactome.
2010 Mar 8
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 17:30:04 GMT 2023
Edited
by admin
on Fri Dec 15 17:30:04 GMT 2023
Record UNII
LER583670J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
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
ADASUVE
Brand 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 Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
NCI_THESAURUS C29710
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: SCHIZOPHRENIA)
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
WHO-VATC QN05AH01
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
WHO-ATC N05AH01
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: BIPOLAR DISORDER)
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
Code System Code Type Description
WIKIPEDIA
LOXAPINE
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
DAILYMED
LER583670J
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
CAS
1977-10-2
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
RXCUI
6475
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY RxNorm
PUBCHEM
3964
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
ECHA (EC/EINECS)
217-835-3
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
HSDB
3111
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
IUPHAR
205
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
DRUG BANK
DB00408
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
DRUG CENTRAL
1613
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
EPA CompTox
DTXSID7023229
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
FDA UNII
LER583670J
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
INN
2610
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
NCI_THESAURUS
C61816
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
MERCK INDEX
m6915
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY Merck Index
MESH
D008152
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
ChEMBL
CHEMBL831
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
SMS_ID
100000092266
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
CHEBI
50841
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
LACTMED
Loxapine
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
PRIMARY
EVMPD
SUB08607MIG
Created by admin on Fri Dec 15 17:30:05 GMT 2023 , Edited by admin on Fri Dec 15 17:30:05 GMT 2023
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
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