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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:: 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
1.3 nM [Ki]
0.06 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

1.25012161E12
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

1.25012161E12
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: Page: p.16
unhealthy, pediatric patients
n = 99
Health Status: unhealthy
Condition: Bipolar Mania
Age Group: pediatric patients
Population Size: 99
Sources: Page: p.16
Disc. AE: Somnolence, Abdominal pain...
AEs leading to
discontinuation/dose reduction:
Somnolence (2%)
Abdominal pain (2%)
Nausea (2%)
Sources: 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: Page: p.12
unhealthy
n = 1953
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Population Size: 1953
Sources: Page: p.12
Disc. AE: Somnolence...
AEs leading to
discontinuation/dose reduction:
Somnolence (0.6%)
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: 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: Page: p.1
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: Page: p.16
unhealthy, pediatric patients
n = 99
Health Status: unhealthy
Condition: Bipolar Mania
Age Group: pediatric patients
Population Size: 99
Sources: Page: p.16
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: Page: p.16
unhealthy, pediatric patients
n = 99
Health Status: unhealthy
Condition: Bipolar Mania
Age Group: pediatric patients
Population Size: 99
Sources: Page: p.16
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: Page: p.16
unhealthy, pediatric patients
n = 99
Health Status: unhealthy
Condition: Bipolar Mania
Age Group: pediatric patients
Population Size: 99
Sources: Page: p.16
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: Page: p.12
unhealthy
n = 1953
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Population Size: 1953
Sources: Page: p.12
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Schizophrenia|Bipolar I disorder
Sources: Page: p.1
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: 24.0
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: 23.0
major
weak (co-administration study)
Comment: fluvoxamine increased cmax of asenapine 13%, auc 29%
Page: 23.0
no
yes
no (co-administration study)
Comment: paroxetine has no effect on asenapine
Page: 30.0
yes
weak (co-administration study)
Comment: cimetidine has no effect on asenapine; carbamazepine has weak effect on asenapine
Page: 30.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients.
2007
Bipolar depression: trial-based insights to guide patient care.
2008
Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.
2008 Feb
Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions.
2009 Jan
Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms.
2009 Jun
Asenapine exerts distinctive regional effects on ionotropic glutamate receptor subtypes in rat brain.
2009 May
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
Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects.
2010 Jul
Asenapine induces differential regional effects on serotonin receptor subtypes.
2010 Mar
Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study.
2010 Nov
New antipsychotic drugs: how do their receptor-binding profiles compare?
2010 Sep
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. 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
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