ASENAPINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H16ClNO
Molecular Weight	285.768
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CN(C)C[C@]1([H])C3=C(OC4=CC=C(Cl)C=C24)C=CC=C3

InChI

InChIKey=VSWBSWWIRNCQIJ-HUUCEWRRSA-N

InChI=1S/C17H16ClNO/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19/h2-8,14-15H,9-10H2,1H3/t14-,15-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C17H16ClNO
Molecular Weight	285.768
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19876039 | https://www.ncbi.nlm.nih.gov/pubmed/18308814

Asenapine is an antipsychotic drug. The mechanism of action of asenapine, as with other drugs having efficacy in schizophrenia and bipolar disorder, is unknown. Asenapine exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors, dopamine D2, D3, D4, and D1 receptors, α1 and α2-adrenergic receptors, and histamine H1 receptors, and moderate affinity for H2 receptors. In in vitro assays asenapine acts as an antagonist at these receptors. It has been suggested that the efficacy of asenapine in schizophrenia is mediated through a combination of antagonist activity at D2 and 5-HT2A receptors. Asenapine is approved by the FDA for the acute treatment of schizophrenia in adults and for the acute treatment of manic or mixed episodes associated with bipolar I disorder, with or without psychotic features, in adults.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
D(2) dopamine receptor 58 Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18308814 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf	Antagonist 2760		1.3 nM [Ki]
5-hydroxytryptamine receptor 2A 69 Target ID: P28223 Gene ID: 3356.0 Gene Symbol: HTR2A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18308814 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf	Antagonist 2760		0.06 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 295 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf	Primary		Approved 8360	SAPHRIS Approved Use SAPHRIS is indicated for the treatment of schizophrenia. SAPHRIS is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder. SAPHRIS is indicated as adjunctive therapy with either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Launch Date 1.25012161E12
Bipolar I disorder (manic or mixed episodes) 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf	Primary		Approved 8360	SAPHRIS Approved Use SAPHRIS is indicated for the treatment of schizophrenia. SAPHRIS is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder. SAPHRIS is indicated as adjunctive therapy with either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Launch Date 1.25012161E12

C_max

Value	Dose	Co-administered	Analyte	Population
4.73 ng/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/epdf/10.1002/gps.2737	5 mg 2 times / day multiple, sublingual dose: 5 mg route of administration: Sublingual experiment type: MULTIPLE co-administered:		ASENAPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
32.1 ng × h/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/epdf/10.1002/gps.2737	5 mg 2 times / day multiple, sublingual dose: 5 mg route of administration: Sublingual experiment type: MULTIPLE co-administered:		ASENAPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
30 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212268s000lbl.pdf	3.8 mg single, transdermal dose: 3.8 mg route of administration: Transdermal experiment type: SINGLE co-administered:		ASENAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212268s000lbl.pdf	3.8 mg single, transdermal dose: 3.8 mg route of administration: Transdermal experiment type: SINGLE co-administered:		ASENAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
10 mg 2 times / day multiple, sublingual Recommended Dose: 10 mg, 2 times / day Route: sublingual Route: multiple Dose: 10 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.16	unhealthy, pediatric patients n = 99 Health Status: unhealthy Condition: Bipolar Mania Age Group: pediatric patients Population Size: 99 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.16	Disc. AE: Somnolence, Abdominal pain... AEs leading to discontinuation/dose reduction: Somnolence (2%) Abdominal pain (2%) Nausea (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.16
10 mg 2 times / day multiple, sublingual Recommended Dose: 10 mg, 2 times / day Route: sublingual Route: multiple Dose: 10 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.12	unhealthy n = 1953 Health Status: unhealthy Condition: Schizophrenia\|Bipolar I disorder Population Size: 1953 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.12	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence (0.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.12
10 mg 2 times / day multiple, sublingual Recommended Dose: 10 mg, 2 times / day Route: sublingual Route: multiple Dose: 10 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Schizophrenia\|Bipolar I disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.1	Disc. AE: Cerebrovascular disorder (NOS), Neuroleptic malignant syndrome... AEs leading to discontinuation/dose reduction: Cerebrovascular disorder (NOS) Neuroleptic malignant syndrome Tardive dyskinesia Orthostatic hypotension Leukopenia Neutropenia Agranulocytosis QT interval prolonged Seizures Cognitive impairment Hyperglycemia Diabetes mellitus Dyslipidemia Weight gain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022117s020s021lbl.pdf Page: p.1

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inducer 768 inhibitor 1579	inhibitor 1752	inhibitor 1837 substrate 1193	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1463 CYP1A2 1509 CYP2C8 901 CYP2A6 704	UGT1A4 347 CYP1A2 1032 P-gp 1527	CYP1A2 689

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	minor [Ki 105 uM]
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	minor [Ki 360 uM]
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 24.0	weak [Ki 0.016 uM]	weak (co-administration study) Comment: asenapine increased exposure of paroxetine by 2x; asenapine had no effect on imipramine in separate study, so paroxetine may be an outlier Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 24.0
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	yes [Ki 1.5 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	yes [Ki 2 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 83.0	yes [Ki 91.4 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A4 347	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 23.0	major	no (co-administration study) Comment: valproate has no effect on asenapine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 23.0
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 23.0	major	weak (co-administration study) Comment: fluvoxamine increased cmax of asenapine 13%, auc 29% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 23.0
P-gp 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 86.0	no
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0	yes	no (co-administration study) Comment: paroxetine has no effect on asenapine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0	yes	weak (co-administration study) Comment: cimetidine has no effect on asenapine; carbamazepine has weak effect on asenapine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 70.0

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0036UH
1PlusChem LLC	1P009CPQ
1PlusChem LLC	1P00E9LQ
A2B Chem	AB48041
AChemBlock	10451
AK Scientific	X2936
AbovChem LLC	HY-11100
AbovChem LLC	HY-16567
ApexBio Technology	A3192
ApexBio Technology	A5010
AstaTech	43030
Axon MedChem	1503
BLD Pharm	BD154848
BLD Pharm	BD630244
BOC Sciences	85650-56-2
Chem Scene	CS-0009346
Chem Scene	CS-0859
Chem Scene	CS-1053
Compound Cloud	163091
Compound Cloud	6917875
Enamine	EN300-123441
Hairui	HR104226
Hairui	HR116489
Hangzhou APIChem Technology	AC-24116
Lab Network	LN01342767
Lab Seeker	SC-82643
MedChem Express	HY-10121
MedChem Express	HY-11100
MedChem Express	HY-16567
MolPort	MolPort-006-133-817
MolPort	MolPort-006-142-524
MolPort	MolPort-023-276-919
MolPort	MolPort-046-417-148
MolPort	MolPort-046-702-063
Molnova	M15492
Molnova	M16209
MuseChem	I000516
MuseChem	I002919
MuseChem	R027114
MuseChem	R027986
MuseChem	R037024
PI Chemicals	PI-37740
ShangHai Biochempartner	BCP05157
Sigma Aldrich	A-101
Sigma Aldrich	A7861
Sigma Aldrich	A7861\|SIGMA
TargetMol	T1951
Tocris	3737
Toronto Research Chemicals	A788000
Toronto Research Chemicals	A788025
Toronto Research Chemicals	M225790
ZINC	ZINC000000002299	http://zinc15.docking.org/substances/ZINC000000002299
eMolecules	106929509
eMolecules	300929760
eMolecules	303168224
eMolecules	31217067
eMolecules	43473206
eNovation Chemicals	D389071
mcule	MCULE-3469383831
mcule	MCULE-4789699486
mcule	MCULE-5342667273
mcule	MCULE-7804068322
mcule	MCULE-8379278884

PubMed

Title	Date	PubMed
Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients.	2007	17285099
Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial.	2007 Oct	17960962
Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.	2008 Feb	17940749
Differential regional and dose-related effects of asenapine on dopamine receptor subtypes.	2008 May	18297468
Asenapine increases dopamine, norepinephrine, and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus.	2008 Nov	18418367
Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder.	2009	19851515
Asenapine maleate: a new drug for the treatment of schizophrenia and bipolar mania.	2009 Dec	20135021
Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.	2009 Jan	18308814
Modeling and simulation of the time course of asenapine exposure response and dropout patterns in acute schizophrenia.	2009 Jul	19387434
Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms.	2009 Jun	19198810
Asenapine exerts distinctive regional effects on ionotropic glutamate receptor subtypes in rat brain.	2009 May	19177511
Asenapine.	2009 Nov	19876039
Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.	2010 Apr	20520283
Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial.	2010 Apr	20096936
Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors.	2010 Apr	19835670
A review of new atypical antipsychotic launches in the United States.	2010 Dec	21274390
Asenapine, a new sublingual atypical antipsychotic.	2010 Jan	21808592
Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects.	2010 Jul	20549835
Long-term assessment of Asenapine vs. Olanzapine in patients with schizophrenia or schizoaffective disorder.	2010 Jun	20205074
Pharmacology and efficacy of asenapine for manic and mixed states in adults with bipolar disorder.	2010 May	20420486
[The quest for the pharmacological treatment of schizophrenia: from conventional neuroleptics to atypical antipsychotics and beyond].	2010 Sep-Oct	21218203

Patents

Sample Use Guides

In Vivo Use Guide

SAPHRIS is a sublingual tablet. To ensure optimal absorption, patients should be instructed to place the tablet under the tongue and allow it to dissolve completely. The tablet will dissolve in saliva within seconds. SAPHRIS sublingual tablets should not be crushed, chewed, or swallowed. Patients should be instructed to not eat or drink for 10 minutes after administration. Schizophrenia Usual Dose for Acute Treatment in Adults: The recommended starting and target dose of SAPHRIS is 5 mg given twice daily. In short term controlled trials, there was no suggestion of added benefit with a 10 mg twice daily dose, but there was a clear increase in certain adverse reactions. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies. Maintenance Treatment: Efficacy was demonstrated with SAPHRIS in a maintenance trial in patients with schizophrenia. The starting dose in this study was 5 mg twice daily with an increase up to 10 mg twice daily after 1 week based on tolerability. While there is no body of evidence available to answer the question of how long the schizophrenic patient should remain on SAPHRIS, patients should be periodically reassessed to determine the need for maintenance treatment. Bipolar Disorder Usual Dose for Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder in Adults: Monotherapy: The recommended starting dose of SAPHRIS, and the dose maintained by 90% of the patients studied, is 10 mg twice daily. The dose can be decreased to 5 mg twice daily if warranted by adverse effects or based on individual tolerability. In controlled monotherapy trials, the starting dose for SAPHRIS was 10 mg twice daily. On the second and subsequent days of the trials, the dose could be lowered to 5 mg twice daily, based on tolerability, but less than 10% of patients had their dose reduced. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials. Adjunctive Therapy: The recommended starting dose of SAPHRIS is 5 mg twice daily when administered as adjunctive therapy with either lithium or valproate. Depending on the clinical response and tolerability in the individual patient, the dose can be increased to 10 mg twice daily. The safety of doses above 10 mg twice daily as adjunctive therapy with lithium or valproate has not been evaluated in clinical trials. Maintenance Treatment: While there is no body of evidence available to answer the question of how long the bipolar patient should remain on SAPHRIS, whether used as monotherapy or as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients be continued beyond the acute response. If SAPHRIS is used for extended periods in bipolar disorder, the physician should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

Route of Administration: Oral

In Vitro Use Guide

like clozapine (100 nM), but at a considerably lower concentration (5 nM), asenapine significantly potentiated the NMDA-induced responses in the rat medial prefrontal cortex pyramidal neurons

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:09:12 UTC 2023` Edited by `admin` on `Wed Jul 05 23:09:12 UTC 2023`
Record UNII	JKZ19V908O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ASENAPINE

Official Name

English

asenapine [INN]

Common Name

English

1H-DIBENZ(2,3:6,7)OXEPINO(4,5-C)PYRROLE, 5-CHLORO-2,3,3A,12B-TETRAHYDRO-2-METHYL-, (3AR,12BR)-REL-

Common Name

English

ASENAPINE [MI]

Common Name

English

ASENAPINE [ORANGE BOOK]

Common Name

English

(3ARS,12BRS)-5-CHLORO-2-METHYL-2,3,3A,12B-TETRAHYDRO-1H-DIBENZO(2,3:6,7)OXEPINO(4,5-C)PYRROLE

Common Name

English

ASENAPINE [VANDF]

Common Name

English

Asenapine [WHO-DD]

Common Name

English

SECUADO

Brand Name

English

Classification Tree Code System Code

NDF-RT

N0000175430