U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H18ClN3O
Molecular Weight 327.8086
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOXAPINE

SMILES

CN1CCN(CC1)C2=Nc3ccccc3Oc4ccc(cc42)Cl

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 327.8086
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
48
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
2575
 18.0 nM [Ki]
D(2) dopamine receptor
57
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
Antagonist
2575
 10.0 nM [Ki]
D(3) dopamine receptor
14
Target ID: P35462
Gene ID: 1814.0
Gene Symbol: DRD3
Target Organism: Homo sapiens (Human)
Antagonist
2575
 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
2575
 9.0 nM [Ki]
Histamine H1 receptor
304
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2575
 15.0 nM [Ki]
Muscarinic acetylcholine receptor M1
160
Target ID: P11229
Gene ID: 1128.0
Gene Symbol: CHRM1
Target Organism: Homo sapiens (Human)
Antagonist
2575
 117.0 nM [Ki]
Alpha-2A adrenergic receptor
24
Target ID: P08913
Gene ID: 150.0
Gene Symbol: ADRA2A
Target Organism: Homo sapiens (Human)
Antagonist
2575
 250.0 nM [Ki]
5-hydroxytryptamine receptor 2A
68
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Antagonist
2575
 2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8043
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

1.62518401E11
Primary
Approved
8043
Adasuve

Approved Use

Schizophrenia

Launch Date

1.3559616E12
Primary
Approved
8043
Adasuve

Approved Use

Bipolar I disorder

Launch Date

1.3559616E12
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
1601

inhibitor
1467
substrate
936

inhibitor
1604
substrate
1118

inhibitor
1702
inhibitor
1475

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1330

CYP1A1
96

CYP1A2
1383

CYP2A6
627

CYP2B6
717

CYP2C8
818

CYP2C19
1325

CYP2E1
790
CYP1A2
972

FMO
33

P-gp
1400

CYP3A4/5
76

CYP2C8
634

CYP2C19
910
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
192
 no
CYP1A2
1532
 no
CYP2A6
659
 no
CYP2B6
884
 no
CYP2C19
1392
 no
CYP2C8
865
 no
CYP2C9
1648
 no
CYP2D6
1738
 no
CYP2E1
871
 no
CYP3A4
1772
 no
P-gp
1514
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
910
 minor
P-gp
1400
 no
no (co-administration study)
Comment: ketoconazole did not affect loxapine transport
Page: 20.0
CYP1A2
972
 yes
CYP2C8
634
 yes
CYP2C9
936
 yes
CYP2D6
1118
 yes
CYP3A4
1601
 yes
CYP3A4/5
76
 yes
FMO
33
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1507
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
Treatment of the special patient with schizophrenia.
2001 Jun
[Survey of management methods for patients in a state of agitation at admission and emergency departments in France].
2003 Mar-Apr
Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake.
2003 May
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.
2003 May
Interspecies variability and drug interactions of loxapine metabolism in liver microsomes.
2003 Oct-Dec
Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors.
2004 Jul 14
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
Treatment of acute mania--from clinical trials to recommendations for clinical practice.
2005 Jan
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
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
[Therapeutics approach of adult patients with acute and chronic psychotic states: REALITE survey].
2006 Jul-Aug
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
Synthesis, characterization, antimicrobial and single crystal X-ray crystallographic studies of some new sulfonyl, 4-chloro phenoxy benzene and dibenzoazepine substituted benzamides.
2006 Nov
Loxapine treatment in an autistic child with aggressive behavior: therapeutic challenges.
2006 Oct
Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review.
2006 Sep
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
Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma.
2007 May
Clozapine: Current perspective.
2007 Oct
Determination of clozapine and its metabolite, norclozapine in various biological matrices using high-performance liquid chromatography.
2007 Oct
HPLC analysis of the novel antidepressant duloxetine in human plasma after an original solid-phase extraction procedure.
2007 Sep 1
Analysis of the recent antipsychotic aripiprazole in human plasma by capillary electrophoresis and high-performance liquid chromatography with diode array detection.
2008 Apr 7
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
Incorporating clinical guidelines through clinician decision-making.
2008 Feb 29
Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia.
2008 Jan
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
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
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
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
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
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 Sat Jun 26 00:09:55 UTC 2021
Edited
by admin
on Sat Jun 26 00:09:55 UTC 2021
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
LOXAPINE [WHO-DD]
Common 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 [ORANGE BOOK]
Common Name English
LOXAPINE [HSDB]
Common Name English
LOXAPINE [MART.]
Common Name English
Classification Tree Code System Code
LIVERTOX 575
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
NCI_THESAURUS C29710
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: SCHIZOPHRENIA)
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
WHO-VATC QN05AH01
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
WHO-ATC N05AH01
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: BIPOLAR DISORDER)
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
Code System Code Type Description
WIKIPEDIA
LOXAPINE
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
CAS
1977-10-2
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
RXCUI
6475
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY RxNorm
PUBCHEM
3964
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
ECHA (EC/EINECS)
217-835-3
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
HSDB
3111
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
IUPHAR
205
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
DRUG BANK
DB00408
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
DRUG CENTRAL
1613
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
EPA CompTox
1977-10-2
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
FDA UNII
LER583670J
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
INN
2610
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
NCI_THESAURUS
C61816
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
MERCK INDEX
M6915
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY Merck Index
MESH
D008152
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL831
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
LACTMED
Loxapine
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
PRIMARY
EVMPD
SUB08607MIG
Created by admin on Sat Jun 26 00:09:56 UTC 2021 , Edited by admin on Sat Jun 26 00:09:56 UTC 2021
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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