Loxapine Succinate

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

SMILES

OC(=O)CCC(O)=O.CN1CCN(CC1)C2=NC3=CC=CC=C3OC4=C2C=C(Cl)C=C4

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	MOL RATIO 1 MOL RATIO (average)

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	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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

Targets

Primary Target	Pharmacology	Potency
D(1A) dopamine receptor 18	Antagonist 2,849	18.0 nM [Ki]
D(2) dopamine receptor 58	Antagonist 2,849	10.0 nM [Ki]
D(3) dopamine receptor 16	Antagonist 2,849	21.0 nM [Ki]
D(4) dopamine receptor 3	Antagonist 2,849	9.0 nM [Ki]
Histamine H1 receptor 316	Antagonist 2,849	15.0 nM [Ki]
Muscarinic acetylcholine receptor M1 168	Antagonist 2,849	117.0 nM [Ki]
Alpha-2A adrenergic receptor 26	Antagonist 2,849	250.0 nM [Ki]
5-hydroxytryptamine receptor 2A 73	Antagonist 2,849	2.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 305	Primary	Approved 8,583	LOXITANE
Schizophrenia 305	Primary	Approved 8,583	Adasuve
Bipolar I disorder 19	Primary	Approved 8,583	Adasuve

C_max

Value	Dose	Co-administered	Analyte	Population
257 ng/mL	10 mg single, respiratory		LOXAPINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
188 ng × h/mL	10 mg single, respiratory		LOXAPINE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.61 h	10 mg single, respiratory		LOXAPINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.4%	10 mg single, respiratory		LOXAPINE plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252	substrate 1,193 inhibitor 2,438	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,741 CYP1A1 132 CYP1A2 2,153 CYP2A6 879 CYP2B6 926 CYP2C8 1,057 CYP2C19 2,057 CYP2E1 1,060	CYP1A2 1,197 FMO 34 P-gp 2,052 CYP3A4/5 91 CYP2C8 810 CYP2C19 1,119

Drug as perpetrator

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Target	Modality	Activity
CYP1A1 272	inhibitor 4,027	no
CYP1A2 2,333	inhibitor 4,027	no
CYP2A6 911	inhibitor 4,027	no
CYP2B6 1,160	inhibitor 4,027	no
CYP2C19 2,141	inhibitor 4,027	no

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP2C19 1,119	substrate 4,014	minor
P-gp 2,052	substrate 4,014	no	no (co-administration study)
CYP1A2 1,197	substrate 4,014	yes
CYP2C8 810	substrate 4,014	yes
CYP2C9 1,193	substrate 4,014	yes

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
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

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PubMed

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Title	Date	PubMed
[Psychiatric manifestations of lupus erythematosus systemic and Sjogren's syndrome].	2001 Nov-Dec	11865567
Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPH.	2002 Jun	12037296
TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243].	2002 Oct 16	12383353
Loxapine versus olanzapine in the treatment of delirium following traumatic brain injury.	2003	14530585
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	12444298

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Patents

Sample Use Guides

In Vivo Use Guide

Adasuve (loxapine inhalation powder), 10 mg by oral inhalation

Route of Administration: Respiratory

In Vitro Use Guide

Unknown

Substance Class	Chemical
Record UNII	X59SG0MRYU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Loxapine Succinate

Official Name

English

LOXITANE

Preferred Name

English

LOXAPINE SUCCINATE [USP-RS]

Common Name

English

Loxapine succinate [WHO-DD]

Common Name

English

LOXAPINE SUCCINATE [USP MONOGRAPH]

Common Name

English

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Classification Tree

Code System

Code

Agent Affecting Nervous System

NCI_THESAURUS

C29710

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Code System

Code

Type

Description

MERCK INDEX

m6915

PRIMARY

Merck Index

RS_ITEM_NUM

1370702

PRIMARY

ECHA (EC/EINECS)

248-682-0

PRIMARY

EPA CompTox

DTXSID3045227

PRIMARY

EVMPD

SUB02977MIG

PRIMARY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator