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

Details

Stereochemistry ACHIRAL
Molecular Formula C18H18ClN3O.ClH
Molecular Weight 364.269
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOXAPINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=JSXBVMKACNEMKY-UHFFFAOYSA-N
InChI=1S/C18H18ClN3O.ClH/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;1H

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 ClH
Molecular Weight 36.461
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
50
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
2760
 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
2760
 10.0 nM [Ki]
D(3) dopamine receptor
17
Target ID: P35462
Gene ID: 1814.0
Gene Symbol: DRD3
Target Organism: Homo sapiens (Human)
Antagonist
2760
 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
2760
 9.0 nM [Ki]
Histamine H1 receptor
313
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2760
 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
2760
 117.0 nM [Ki]
Alpha-2A adrenergic receptor
25
Target ID: P08913
Gene ID: 150.0
Gene Symbol: ADRA2A
Target Organism: Homo sapiens (Human)
Antagonist
2760
 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
2760
 2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8360
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
8360
Adasuve

Approved Use

Schizophrenia

Launch Date

1.3559616E12
Primary
Approved
8360
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
1709

inhibitor
1579
substrate
1010

inhibitor
1752
substrate
1193

inhibitor
1837
inhibitor
1599

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1437

CYP1A1
110

CYP1A2
1509

CYP2A6
704

CYP2B6
799

CYP2C8
901

CYP2C19
1463

CYP2E1
876
CYP1A2
1032

FMO
35

P-gp
1527

CYP3A4/5
85

CYP2C8
688

CYP2C19
985
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
218
 no
CYP1A2
1673
 no
CYP2A6
736
 no
CYP2B6
985
 no
CYP2C19
1537
 no
CYP2C8
955
 no
CYP2C9
1803
 no
CYP2D6
1875
 no
CYP2E1
964
 no
CYP3A4
1909
 no
P-gp
1626
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
985
 minor
P-gp
1527
 no
no (co-administration study)
Comment: ketoconazole did not affect loxapine transport
Page: 20.0
CYP1A2
1032
 yes
CYP2C8
688
 yes
CYP2C9
1010
 yes
CYP2D6
1193
 yes
CYP3A4
1709
 yes
CYP3A4/5
85
 yes
FMO
35
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1632
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
Does loxapine have "atypical" properties? Clinical evidence.
1999
Olanzapine-induced tardive dystonia.
1999 Oct
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.
2000 Oct
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
Loxapine side-effects: 3 case reports of hyperleukocytosis.
2001 Jan-Feb
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
Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study.
2002
Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation.
2002 Apr
[Self-poisoning with Datura stramonium. 3 case reports].
2002 Jan 19
Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPH.
2002 Jun
Discriminative stimulus properties in rats of the novel antipsychotic quetiapine.
2002 Nov
TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243].
2002 Oct 16
Human genetic variations in the 5HT2A receptor: a single nucleotide polymorphism identified with altered response to clozapine.
2003 Feb
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
[Survey of management methods for patients in a state of agitation at admission and emergency departments in France].
2003 Mar-Apr
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
An assessment of quality of sleep and the use of drugs with sedating properties in hospitalized adult patients.
2004 Mar 24
Minimally effective doses of conventional antipsychotic medications used to treat aggression, self-injurious and destructive behaviors in mentally retarded adults.
2005 Feb
Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up.
2006 Jun
Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients.
2006 Nov
Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.
2007 Apr
Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients.
2007 Feb 27
HPLC analysis of the novel antidepressant duloxetine in human plasma after an original solid-phase extraction procedure.
2007 Sep 1
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
Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N-desmethyl clozapine (norclozapine) in human serum.
2009
Safety and efficacy of antipsychotic drugs for the behavioral and psychological symptoms of dementia.
2009 Jan
Current perspectives in the treatment of resistant schizophrenia.
2009 Oct-Dec
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
An overview of Indian research in schizophrenia.
2010 Jan
Simultaneous HPLC determination of 14 tricyclic antidepressants and metabolites in human plasma.
2010 Jan
4-Nitro-2-phenoxy-aniline.
2010 May 8
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 Wed Jul 05 23:52:23 UTC 2023
Edited
by admin
on Wed Jul 05 23:52:23 UTC 2023
Record UNII
376MYL4MAL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOXAPINE HYDROCHLORIDE
MART.   ORANGE BOOK   VANDF   WHO-DD  
Common Name English
Loxapine hydrochloride [WHO-DD]
Common Name English
LOXITANE C
Brand Name English
LOXAPINE HYDROCHLORIDE [MART.]
Common Name English
LOXAPINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
LOXAPINE HCL
Common Name English
LOXAPINE HYDROCHLORIDE [VANDF]
Common Name English
LOXITANE IM
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C66885
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
NCI_THESAURUS C66883
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL831
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
EVMPD
SUB22686
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
NCI_THESAURUS
C77574
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
PUBCHEM
71400
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
WIKIPEDIA
Loxapine hydrochloride
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
FDA UNII
376MYL4MAL
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
SMS_ID
100000088112
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
DRUG BANK
DBSALT001429
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
CAS
54810-23-0
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
EPA CompTox
DTXSID70203304
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY
RXCUI
91138
Created by admin on Wed Jul 05 23:52:23 UTC 2023 , Edited by admin on Wed Jul 05 23:52:23 UTC 2023
PRIMARY RxNorm
Related Record Type Details
Structure of LOXAPINE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of LOXAPINE
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