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 2778		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 2778		0.06 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf	Primary		Approved 8429	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 2009
Bipolar I disorder (manic or mixed episodes) 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022117s010lbl.pdf	Primary		Approved 8429	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 2009

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 1737 inducer 781 inhibitor 1587	inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP1A2 1524 CYP2C8 911 CYP2A6 707	UGT1A4 347 CYP1A2 1054 P-gp 1537	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	minor [Ki 105 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	minor [Ki 360 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022117s000lbl.pdf Page: 30.0	no
CYP2D6 1891	inhibitor 3277 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 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	yes [Ki 1.5 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 84.0	yes [Ki 2 uM]
CYP3A4 1925	inhibitor 3277 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 3367 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 1054	substrate 3367 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 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_PharmR.pdf Page: 86.0	no
CYP2D6 1217	substrate 3367 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 1737	substrate 3367 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 1647	inhibitor 1626 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
Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.	2008 Feb	17940749
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 for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic.	2009 Dec	19840150
Asenapine versus olanzapine in acute mania: a double-blind extension study.	2009 Dec	19832806
Asenapine.	2009 Nov	19876039
Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation.	2009 Nov	19843656
A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states.	2009 Nov	19839993
Asenapine effects in animal models of psychosis and cognitive function.	2009 Nov	19462162
Asenapine approved for treatment of schizophrenia, bipolar disorder.	2009 Sep 15	19729558
Neuroleptic malignant syndrome after exposure to asenapine: a case report.	2010	21274350
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
Evaluation of the clinical efficacy of asenapine in schizophrenia.	2010 Aug	20642375
A review of new atypical antipsychotic launches in the United States.	2010 Dec	21274390
Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat.	2010 Dec 25	20561963
Asenapine (Saphris) sublingual tablets for schizophrenia and bipolar disorder.	2010 Feb 8	20216523
Asenapine, a new sublingual atypical antipsychotic.	2010 Jan	21808592
New drugs: asenapine, iloperidone, and bepotastine besilate.	2010 Jan-Feb	20097650
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
New drug information. Saphris.	2010 Mar	20232719
Effects of asenapine on prefrontal N-methyl-D-aspartate receptor-mediated transmission: involvement of dopamine D1 receptors.	2010 Nov	20842721
Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study.	2010 Nov	20537396
A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder.	2010 Nov 19	21092101
New antipsychotic drugs: how do their receptor-binding profiles compare?	2010 Sep	20923625
Adjunctive use of atypical antipsychotics for treatment-resistant generalized anxiety disorder.	2010 Sep	20795849
[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 `Fri Dec 15 15:40:11 GMT 2023` Edited by `admin` on `Fri Dec 15 15:40:11 GMT 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