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

Details

Stereochemistry ACHIRAL
Molecular Formula C18H18ClN3O.C4H6O4
Molecular Weight 445.896
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOXAPINE SUCCINATE

SMILES

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

InChI

InChIKey=YQZBAXDVDZTKEQ-UHFFFAOYSA-N
InChI=1S/C18H18ClN3O.C4H6O4/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;5-3(6)1-2-4(7)8/h2-7,12H,8-11H2,1H3;1-2H2,(H,5,6)(H,7,8)

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 C4H6O4
Molecular Weight 118.088
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
49
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
2737
 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
2737
 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
2737
 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
2737
 9.0 nM [Ki]
Histamine H1 receptor
312
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2737
 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
2737
 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
2737
 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
2737
 2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8307
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
8307
Adasuve

Approved Use

Schizophrenia

Launch Date

1.3559616E12
Primary
Approved
8307
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
1670

inhibitor
1532
substrate
985

inhibitor
1695
substrate
1168

inhibitor
1789
inhibitor
1570

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1401

CYP1A1
104

CYP1A2
1463

CYP2A6
670

CYP2B6
770

CYP2C8
869

CYP2C19
1410

CYP2E1
846
CYP1A2
1013

FMO
35

P-gp
1491

CYP3A4/5
82

CYP2C8
670

CYP2C19
955
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
206
 no
CYP1A2
1620
 no
CYP2A6
702
 no
CYP2B6
946
 no
CYP2C19
1484
 no
CYP2C8
923
 no
CYP2C9
1747
 no
CYP2D6
1826
 no
CYP2E1
929
 no
CYP3A4
1857
 no
P-gp
1588
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
955
 minor
P-gp
1491
 no
no (co-administration study)
Comment: ketoconazole did not affect loxapine transport
Page: 20.0
CYP1A2
1013
 yes
CYP2C8
670
 yes
CYP2C9
985
 yes
CYP2D6
1168
 yes
CYP3A4
1670
 yes
CYP3A4/5
82
 yes
FMO
35
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1603
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
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
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
[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
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
Simultaneous determination of four antipsychotic drugs in plasma by high-performance liquid chromatography. Application to management of acute intoxications.
2003 Oct 5
JL 13, an atypical antipsychotic: a preclinical review.
2003 Spring
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
[Agranulocytosis induced by loxapine in an elderly patient: a case study].
2004 Sep-Oct
Atypical and typical antipsychotic drug interactions with the dopamine D2 receptor.
2005 Feb
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
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
NMS after clozapine initiation.
2005 Nov
Lack of enhanced effect of antipsychotics combined with fluvoxamine on acetylcholine release in rat prefrontal cortex.
2006 Dec
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
Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review.
2006 Sep
Effect of loxapine on electrical brain activity, intracranial pressure, and middle cerebral artery flow velocity in traumatic brain-injured patients.
2007
Simultaneous determination of the antipsychotic drugs levomepromazine and clozapine and their main metabolites in human plasma by a HPLC-UV method with solid-phase extraction.
2007 Feb 1
Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma.
2007 May
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
Modifications of antiepileptic drugs for improved tolerability and efficacy.
2008 Feb 14
Incorporating clinical guidelines through clinician decision-making.
2008 Feb 29
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
Spectroscopic and electrochemical analysis of psychotropic drugs.
2009 Jan
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
Current perspectives in the treatment of resistant schizophrenia.
2009 Oct-Dec
Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation.
2010
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
Simultaneous HPLC determination of 14 tricyclic antidepressants and metabolites in human plasma.
2010 Jan
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
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 Fri Dec 16 17:32:14 UTC 2022
Edited
by admin
on Fri Dec 16 17:32:14 UTC 2022
Record UNII
X59SG0MRYU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOXAPINE SUCCINATE
MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
LOXAPINE SUCCINATE [USP-RS]
Common Name English
Loxapine succinate [WHO-DD]
Common Name English
LOXAPINE SUCCINATE [USP MONOGRAPH]
Common Name English
LOXAPINE SUCCINATE [ORANGE BOOK]
Common Name English
LOXAPINE SUCCINATE [MART.]
Common Name English
NSC-759578
Code English
CL 71563
Code English
LOXAPINE SUCCINATE [VANDF]
Common Name English
LOXAPINE SUCCINATE [USAN]
Common Name English
CL-71563
Code English
LOXAPINE SUCCINATE [MI]
Common Name English
LOXITANE
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C29710
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
Code System Code Type Description
MERCK INDEX
M6915
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY Merck Index
RS_ITEM_NUM
1370702
Created by admin on Fri Dec 16 17:32:15 UTC 2022 , Edited by admin on Fri Dec 16 17:32:15 UTC 2022
PRIMARY
ECHA (EC/EINECS)
248-682-0
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
EPA CompTox
DTXSID3045227
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
EVMPD
SUB02977MIG
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
NSC
759578
Created by admin on Fri Dec 16 17:32:15 UTC 2022 , Edited by admin on Fri Dec 16 17:32:15 UTC 2022
PRIMARY
NCI_THESAURUS
C47590
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
CAS
27833-64-3
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
DAILYMED
X59SG0MRYU
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
DRUG BANK
DBSALT001194
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
PUBCHEM
71399
Created by admin on Fri Dec 16 17:32:15 UTC 2022 , Edited by admin on Fri Dec 16 17:32:15 UTC 2022
PRIMARY
ChEMBL
CHEMBL831
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
RXCUI
6476
Created by admin on Fri Dec 16 17:32:15 UTC 2022 , Edited by admin on Fri Dec 16 17:32:15 UTC 2022
PRIMARY RxNorm
FDA UNII
X59SG0MRYU
Created by admin on Fri Dec 16 17:32:14 UTC 2022 , Edited by admin on Fri Dec 16 17:32:14 UTC 2022
PRIMARY
Related Record Type Details
Structure of LOXAPINE
PARENT -> SALT/SOLVATE
Structure of SUCCINIC ACID
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of 3-CHLORO-11-(4-METHYLPIPERAZIN-1-YL)DIBENZO(B,F)(1,4)OXAZEPINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of AMOXAPINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of 2-CHLORODIBENZO(B,F)-1,4-OXAZEPIN-11-ONE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of LOXAPINE
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966