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

Details

Stereochemistry RACEMIC
Molecular Formula C17H16ClNO
Molecular Weight 285.7686
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ASENAPINE

SMILES

CN1C[C@]2([H])c3ccccc3Oc4ccc(cc4[C@@]2([H])C1)Cl

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

Description
Curator's Comment:: 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P14416
Gene ID: 1813
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
1.30000000000000004 nM [Ki]
0.0599999999999999978 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1250121600000
Primary
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

1250121600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.73 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
32.1 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
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

Doses

DosePopulationAdverse 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:
unhealthy, pediatric patients
Health Status: unhealthy
Age Group: pediatric patients
Sources:
Disc. AE: Somnolence, Abdominal pain...
AEs leading to
discontinuation/dose reduction:
Somnolence (2%)
Abdominal pain (2%)
Nausea (2%)
Sources:
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:
unhealthy
Disc. AE: Somnolence...
AEs leading to
discontinuation/dose reduction:
Somnolence (0.6%)
Sources:
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:
unhealthy
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:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 2%
Disc. AE
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:
unhealthy, pediatric patients
Health Status: unhealthy
Age Group: pediatric patients
Sources:
Nausea 2%
Disc. AE
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:
unhealthy, pediatric patients
Health Status: unhealthy
Age Group: pediatric patients
Sources:
Somnolence 2%
Disc. AE
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:
unhealthy, pediatric patients
Health Status: unhealthy
Age Group: pediatric patients
Sources:
Somnolence 0.6%
Disc. AE
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:
unhealthy
Agranulocytosis Disc. AE
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:
unhealthy
Cerebrovascular disorder (NOS) Disc. AE
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:
unhealthy
Cognitive impairment Disc. AE
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:
unhealthy
Diabetes mellitus Disc. AE
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:
unhealthy
Dyslipidemia Disc. AE
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:
unhealthy
Hyperglycemia Disc. AE
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:
unhealthy
Leukopenia Disc. AE
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:
unhealthy
Neuroleptic malignant syndrome Disc. AE
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:
unhealthy
Neutropenia Disc. AE
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:
unhealthy
Orthostatic hypotension Disc. AE
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:
unhealthy
QT interval prolonged Disc. AE
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:
unhealthy
Seizures Disc. AE
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:
unhealthy
Tardive dyskinesia Disc. AE
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:
unhealthy
Weight gain Disc. AE
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:
unhealthy
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minor [Ki 105 uM]
minor [Ki 360 uM]
no
no
no
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
Page: 24
yes [Ki 1.5 uM]
yes [Ki 2 uM]
yes [Ki 91.4 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
no (co-administration study)
Comment: valproate has no effect on asenapine
Page: 23
major
weak (co-administration study)
Comment: fluvoxamine increased cmax of asenapine 13%, auc 29%
Page: 23
no
yes
no (co-administration study)
Comment: paroxetine has no effect on asenapine
Page: 30
yes
weak (co-administration study)
Comment: cimetidine has no effect on asenapine; carbamazepine has weak effect on asenapine
Page: 30
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Asenapine in the treatment of negative symptoms of schizophrenia: clinical trial design and rationale.
2007
Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients.
2007
Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial.
2007 Oct
Acute and long-term treatment of mania.
2008
Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.
2008 Feb
Actions of novel agonists, antagonists and antipsychotic agents at recombinant rat 5-HT6 receptors: a comparative study of coupling to G alpha s.
2008 Jul 7
American psychiatric association.
2008 Jun
Differential regional and dose-related effects of asenapine on dopamine receptor subtypes.
2008 May
Asenapine increases dopamine, norepinephrine, and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus.
2008 Nov
Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder.
2009
Asenapine maleate: a new drug for the treatment of schizophrenia and bipolar mania.
2009 Dec
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
Asenapine versus olanzapine in acute mania: a double-blind extension study.
2009 Dec
Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions.
2009 Jan
Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.
2009 Jan
Modeling and simulation of the time course of asenapine exposure response and dropout patterns in acute schizophrenia.
2009 Jul
Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms.
2009 Jun
Electrophysiological characterization of the effects of asenapine at 5-HT(1A), 5-HT(2A), alpha(2)-adrenergic and D(2) receptors in the rat brain.
2009 Mar
Asenapine exerts distinctive regional effects on ionotropic glutamate receptor subtypes in rat brain.
2009 May
Asenapine.
2009 Nov
Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation.
2009 Nov
A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states.
2009 Nov
Asenapine effects in animal models of psychosis and cognitive function.
2009 Nov
Asenapine.
2009 Sep
Neuroleptic malignant syndrome after exposure to asenapine: a case report.
2010
Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial.
2010 Apr
Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors.
2010 Apr
Evaluation of the clinical efficacy of asenapine in schizophrenia.
2010 Aug
Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat.
2010 Dec 25
Asenapine (Saphris) sublingual tablets for schizophrenia and bipolar disorder.
2010 Feb 8
Asenapine, a new sublingual atypical antipsychotic.
2010 Jan
New drugs: asenapine, iloperidone, and bepotastine besilate.
2010 Jan-Feb
Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects.
2010 Jul
Long-term assessment of Asenapine vs. Olanzapine in patients with schizophrenia or schizoaffective disorder.
2010 Jun
New drug information. Saphris.
2010 Mar
Effects of asenapine on prefrontal N-methyl-D-aspartate receptor-mediated transmission: involvement of dopamine D1 receptors.
2010 Nov
Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study.
2010 Nov
A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder.
2010 Nov 19
New antipsychotic drugs: how do their receptor-binding profiles compare?
2010 Sep
Adjunctive use of atypical antipsychotics for treatment-resistant generalized anxiety disorder.
2010 Sep
[The quest for the pharmacological treatment of schizophrenia: from conventional neuroleptics to atypical antipsychotics and beyond].
2010 Sep-Oct
Patents

Sample Use Guides

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.
Route of Administration: Oral
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
Name Type Language
ASENAPINE
DASH   INN   MI   VANDF   WHO-DD  
INN  
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 [WHO-DD]
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
SECUADO
Brand Name English
Classification Tree Code System Code
NDF-RT N0000175430
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
WHO-ATC N05AH05
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
NCI_THESAURUS C29710
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
LIVERTOX 66
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
WHO-VATC QN05AH05
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
Code System Code Type Description
EPA CompTox
65576-45-6
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
MERCK INDEX
M2091
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB06216
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL3187365
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
PUBCHEM
163091
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
EVMPD
SUB30497
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
HSDB
8061
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
MESH
C522667
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
FDA UNII
JKZ19V908O
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
RXCUI
784649
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
4115
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
CAS
65576-45-6
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
NCI_THESAURUS
C72705
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
LACTMED
Asenapine
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
IUPHAR
22
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
INN
8278
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY
ECHA (EC/EINECS)
265-829-4
Created by admin on Sat Jun 26 01:21:43 UTC 2021 , Edited by admin on Sat Jun 26 01:21:43 UTC 2021
PRIMARY