Identification

Name
Asenapine
Accession Number
DB06216
Type
Small Molecule
Groups
Approved
Description

Developed by Schering-Plough after its merger with Organon International, asenapine is a sublingually administered, atypical antipsychotic for treatment of schizophrenia and acute mania associated with bipolar disorder. Asenapine also belongs to the dibenzo-oxepino pyrrole class. It is also for severe post-traumatic stress disorder nightmares in soldiers as an off-label use. FDA approved on August 13, 2009.

Structure
Thumb
Synonyms
  • asenapina
External IDs
ORG-5222
Product Ingredients
IngredientUNIICASInChI Key
Asenapine MaleateCU9463U2E285650-56-2GMDCDXMAFMEDAG-CHHFXETESA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SaphrisTablet5 mg/1SublingualAllergan, Inc.2013-09-30Not applicableUs
SaphrisTablet5 mgSublingualMerck Ltd.2011-12-19Not applicableCanada
SaphrisTablet5 mg/1SublingualForest Laboratories, Inc.2013-09-302015-01-01Us
SaphrisTablet5 mg/1SublingualOrganon2010-06-21Not applicableUs
SaphrisTablet10 mg/1SublingualStat Rx USA2009-08-14Not applicableUs
SaphrisTablet2.5 mg/1SublingualAllergan, Inc.2014-12-30Not applicableUs
SaphrisTablet10 mg/1SublingualOrganon2009-08-13Not applicableUs
SaphrisTablet10 mg/1SublingualAllergan, Inc.2013-09-30Not applicableUs
SaphrisTablet10 mgSublingualMerck Ltd.2011-12-19Not applicableCanada
SaphrisTablet10 mg/1SublingualForest Laboratories, Inc.2013-09-302015-01-01Us
International/Other Brands
Saphris / Sycrest (Lundbeck )
Categories
UNII
JKZ19V908O
CAS number
65576-45-6
Weight
Average: 401.84
Monoisotopic: 401.103000462
Chemical Formula
C21H20ClNO5
InChI Key
GMDCDXMAFMEDAG-BTJKTKAUSA-N
InChI
InChI=1S/C17H16ClNO.C4H4O4/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19;5-3(6)1-2-4(7)8/h2-8,14-15H,9-10H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-
IUPAC Name
(2Z)-but-2-enedioic acid; 17-chloro-4-methyl-13-oxa-4-azatetracyclo[12.4.0.0²,⁶.0⁷,¹²]octadeca-1(14),7,9,11,15,17-hexaene
SMILES
OC(=O)\C=C/C(O)=O.CN1CC2C(C1)C1=C(OC3=CC=CC=C23)C=CC(Cl)=C1

Pharmacology

Indication

Used for treatment in psychosis, schizophrenia and schizoaffective disorders, manic disorders, and bipolar disorders as monotherapy or in combination.

Associated Conditions
Pharmacodynamics

Asenapine is a serotonin, dopamine, noradrenaline, and histamine antagonist in which asenapine possess more potent activity with serotonin receptors than dopamine. Sedation in patients is associated with asenapine's antagonist activity at histamine receptors. Its lower incidence of extrapyramidal effects are associated with the upregulation of D1 receptors. This upregulation occurs due to asenapine's dose-dependent effects on glutamate transmission in the brain. It does not have any significant activity with muscarinic, cholinergic receptors therefore symptoms associated with anticholinergic drug activity like dry mouth or constipation are not expected to be observed. Asenapine has a higher affinity for all aforementioned receptors compared to first-generation and second-generation antipsychotics except for 5-HT1A and 5-HT1B receptors.

Mechanism of action

Asenapine is an atypical antipsychotic multireceptor neuroleptic drug which shows strong 5HT2A (serotonin) and D2 (dopamine) receptor antagonism, which has been shown to enhance dopamine (DA) and acetylcholine (Ach) efflux in rat brains. Asenapine may improve cognitive function and negative symptoms in patients with schizophrenia.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
U5-hydroxytryptamine receptor 1B
antagonist
Human
U5-hydroxytryptamine receptor 2B
antagonist
Human
U5-hydroxytryptamine receptor 2C
antagonist
Human
U5-hydroxytryptamine receptor 5A
antagonist
Human
U5-hydroxytryptamine receptor 6
antagonist
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UD(1A) dopamine receptor
antagonist
Human
UD(3) dopamine receptor
antagonist
Human
UD(4) dopamine receptor
antagonist
Human
UHistamine H1 receptor
antagonist
Human
UHistamine H2 receptor
antagonist
Human
UBeta-1 adrenergic receptor
antagonist
Human
UBeta-2 adrenergic receptor
antagonist
Human
Absorption

Cmax, single 5 mg dose = 4 ng/mL (within 1 hour); Bioavailability, sublingual administration = 35%; Bioavailability, oral administration (swallowed) = <2%; Time to steady state, 5 mg = 3 days; Peak plasma concentration occurs within 0.5 to 1.5 hours. Doubling dose of asenapine results in 1.7-fold increase in maximum concentration and exposure. Drinking water within 2-5 minutes post administration of asenapine results in a decrease in exposure.

Volume of distribution

20-25 L/kg

Protein binding

95% protein bound

Metabolism

Asenapine is oxidized via CYP1A2 and undergoes direct glucuronidation via UGT1A4. Oxidation via CYP1A2 is asenapine's primary mode of metabolism.

Route of elimination

Urine (50%) and feces (50%)

Half life

24 hours (range of 13.4 - 39.2 hours)

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Asenapine.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Asenapine is combined with (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Asenapine.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Asenapine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Asenapine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Asenapine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Asenapine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Asenapine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Asenapine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Asenapine.
Food Interactions
  • Avoid water and food for at least 10 minutes post administration of asenapine

References

Synthesis Reference
US4145434
General References
  1. Huang M, Li Z, Dai J, Shahid M, Wong EH, Meltzer HY: Asenapine increases dopamine, norepinephrine, and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus. Neuropsychopharmacology. 2008 Nov;33(12):2934-45. doi: 10.1038/npp.2008.20. Epub 2008 Apr 16. [PubMed:18418367]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
  3. Franberg O, Wiker C, Marcus MM, Konradsson A, Jardemark K, Schilstrom B, Shahid M, Wong EH, Svensson TH: Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia. Psychopharmacology (Berl). 2008 Feb;196(3):417-29. Epub 2007 Oct 17. [PubMed:17940749]
  4. Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F: Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. [PubMed:23356509]
External Links
KEGG Drug
D02995
PubChem Compound
11954293
PubChem Substance
175427062
ChemSpider
10128588
ChEBI
71253
ChEMBL
CHEMBL3544974
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Asenapine
ATC Codes
N05AH05 — Asenapine
AHFS Codes
  • 28:16.08.04 — Atypical Antipsychotics
FDA label
Download (448 KB)
MSDS
Download (91.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableBipolar Disorder (BD) / Schizophrenic Disorders1
1CompletedTreatmentBipolar I Disorder / Schizophrenic Disorders1
2CompletedOtherPsychosis1
2RecruitingTreatmentDepression, Bipolar1
3CompletedTreatmentBipolar 1 Disorder2
3CompletedTreatmentBipolar Disorder (BD)7
3CompletedTreatmentBipolar Disorder, Pediatric1
3CompletedTreatmentBipolar I Disorder1
3CompletedTreatmentPsychosis1
3CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders2
3CompletedTreatmentSchizophrenia, Disorganized / Schizophrenia, paranoid type / Schizophrenia, Undifferentiated2
3CompletedTreatmentSchizophrenic Disorders15
3SuspendedTreatmentStuttering1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedTreatmentAcute Agitation1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentMajor Depressive Disorder Without Psychotic Features1
4CompletedTreatmentPosttraumatic Stress Disorders1
4CompletedTreatmentPsychotic Disorder NOS1
4CompletedTreatmentSchizophrenic Disorders1
4Unknown StatusTreatmentDisorders / Schizophrenia and Disorders With Psychotic Features1
Not AvailableCompletedNot AvailableBipolar Disorder (BD)1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletSublingual10 mg
TabletSublingual10 mg/1
TabletSublingual2.5 mg/1
TabletSublingual5 mg
TabletSublingual5 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5763476Yes1998-06-092020-12-09Us
US7741358Yes2010-06-222026-10-06Us
US8022228Yes2011-09-202026-10-06Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP3.72ChemAxon
pKa (Strongest Basic)7.29ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity81.65 m3·mol-1ChemAxon
Polarizability30.9 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9849
Blood Brain Barrier+0.8842
Caco-2 permeable+0.5605
P-glycoprotein substrateSubstrate0.7617
P-glycoprotein inhibitor INon-inhibitor0.9375
P-glycoprotein inhibitor IINon-inhibitor0.8901
Renal organic cation transporterNon-inhibitor0.7054
CYP450 2C9 substrateNon-substrate0.7964
CYP450 2D6 substrateNon-substrate0.7864
CYP450 3A4 substrateSubstrate0.5065
CYP450 1A2 substrateNon-inhibitor0.5212
CYP450 2C9 inhibitorNon-inhibitor0.7185
CYP450 2D6 inhibitorNon-inhibitor0.6781
CYP450 2C19 inhibitorNon-inhibitor0.5762
CYP450 3A4 inhibitorNon-inhibitor0.8625
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6005
Ames testNon AMES toxic0.5417
CarcinogenicityNon-carcinogens0.8694
BiodegradationNot ready biodegradable0.9894
Rat acute toxicity2.7083 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8125
hERG inhibition (predictor II)Non-inhibitor0.6697
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzoxepines. These are compounds containing a dibenzoxepine moiety, which consists of two benzene connected by an oxazepine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzoxepines
Sub Class
Dibenzoxepines
Direct Parent
Dibenzoxepines
Alternative Parents
Diarylethers / Aralkylamines / Unsaturated fatty acids / Aryl chlorides / N-alkylpyrrolidines / Benzenoids / Dicarboxylic acids and derivatives / Trialkylamines / Oxacyclic compounds / Azacyclic compounds
show 6 more
Substituents
Dibenzoxepine / Diaryl ether / Aralkylamine / Aryl chloride / Aryl halide / Dicarboxylic acid or derivatives / Unsaturated fatty acid / N-alkylpyrrolidine / Benzenoid / Fatty acid
show 21 more
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Tadori Y, Forbes RA, McQuade RD, Kikuchi T: Functional potencies of dopamine agonists and antagonists at human dopamine D(2) and D(3) receptors. Eur J Pharmacol. 2011 Sep;666(1-3):43-52. doi: 10.1016/j.ejphar.2011.05.050. Epub 2011 Jun 1. [PubMed:21658377]
  3. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  3. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  3. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR5A
Uniprot ID
P47898
Uniprot Name
5-hydroxytryptamine receptor 5A
Molecular Weight
40254.69 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  3. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Tadori Y, Forbes RA, McQuade RD, Kikuchi T: Functional potencies of dopamine agonists and antagonists at human dopamine D(2) and D(3) receptors. Eur J Pharmacol. 2011 Sep;666(1-3):43-52. doi: 10.1016/j.ejphar.2011.05.050. Epub 2011 Jun 1. [PubMed:21658377]
  3. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  3. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F: Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. [PubMed:23356509]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F: Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. [PubMed:23356509]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [PubMed:18308814]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
  2. Citrome L: Asenapine review, part I: chemistry, receptor affinity profile, pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol. 2014 Jun;10(6):893-903. doi: 10.1517/17425255.2014.908185. Epub 2014 May 3. [PubMed:24793403]
  3. Asenapine FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Citrome L: Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:325-39. doi: 10.2147/NDT.S16077. Epub 2011 May 26. [PubMed:21655346]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F: Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. [PubMed:23356509]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F: Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. [PubMed:23356509]

Drug created on March 19, 2008 10:17 / Updated on November 17, 2018 07:21