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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
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
Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography.
1991 Mar 8
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
Discriminative stimulus properties in rats of the novel antipsychotic quetiapine.
2002 Nov
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
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.
2003 Mar
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
Neuroleptic malignant syndrome: case report and discussion.
2003 Sep 2
Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors.
2004 Jul 14
Treatment-refractory schizophrenia.
2004 Mar
Minimally effective doses of conventional antipsychotic medications used to treat aggression, self-injurious and destructive behaviors in mentally retarded adults.
2005 Feb
Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures.
2005 Jan
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia.
2006 Feb 21
[Therapeutics approach of adult patients with acute and chronic psychotic states: REALITE survey].
2006 Jul-Aug
[Clinical and socio-demographic profile of patients with schizophrenia according to the antipsychotic treatment prescribed].
2006 May-Jun
Correlations between weight changes and lipid profile changes in schizophrenic patients after antipsychotics therapy.
2007 Jan-Feb
Pharmacological causes of hyperprolactinemia.
2007 Oct
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
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
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
Neuroanatomical, neurochemical, and neurodevelopmental basis of obsessive-compulsive symptoms in schizophrenia.
2009 Jan
Spectroscopic and electrochemical analysis of psychotropic drugs.
2009 Jan
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
[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
Pharmacological interventions for borderline personality disorder.
2010 Jun 16
Identifying unexpected therapeutic targets via chemical-protein interactome.
2010 Mar 8
Chem2Bio2RDF: a semantic framework for linking and data mining chemogenomic and systems chemical biology data.
2010 May 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 Thu Jul 06 00:49:30 UTC 2023
Edited
by admin
on Thu Jul 06 00:49:30 UTC 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 Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
NCI_THESAURUS C29710
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: SCHIZOPHRENIA)
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
WHO-VATC QN05AH01
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
WHO-ATC N05AH01
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
EMA ASSESSMENT REPORTS ADASUVE (AUTHORIZED: BIPOLAR DISORDER)
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
Code System Code Type Description
WIKIPEDIA
LOXAPINE
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
DAILYMED
LER583670J
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
CAS
1977-10-2
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
RXCUI
6475
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY RxNorm
PUBCHEM
3964
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
ECHA (EC/EINECS)
217-835-3
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
HSDB
3111
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
IUPHAR
205
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
DRUG BANK
DB00408
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
DRUG CENTRAL
1613
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
EPA CompTox
DTXSID7023229
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
FDA UNII
LER583670J
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
INN
2610
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
NCI_THESAURUS
C61816
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
MERCK INDEX
M6915
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY Merck Index
MESH
D008152
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
ChEMBL
CHEMBL831
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
SMS_ID
100000092266
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
CHEBI
50841
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
LACTMED
Loxapine
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 2023
PRIMARY
EVMPD
SUB08607MIG
Created by admin on Thu Jul 06 00:49:30 UTC 2023 , Edited by admin on Thu Jul 06 00:49:30 UTC 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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