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Identification
Name Risperidone
Accession Number DB00734 (APRD00187)
Type small molecule
Groups approved
Description

Risperidone, a benzisoxazole derivative, is an atypical antipsychotic drug with high affinity for 5-hydrotryptamine (5-HT) and dopamine D2 receptors. It is used primarily in the management of schizophrenia, inappropriate behavior in severe dementia and manic episodes associated with bipolar I disorder. Risperidone is effective for treating the positive and negative symptoms of schizophrenia owing to its affinity for its “loose” binding affinity for dopamine D2 receptors and additional 5-HT antagonism compared to first generation antipsychotics, which are strong, non-specific dopamine D2 receptor antagonists.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • risperdone
  • Risperidona [Spanish]
  • risperidone
  • Risperidonum [Latin]
Brand names
  • Risperdal (Janssen)
  • Risperdal Consta (Janssen)
  • Risperdal M-Tab (Janssen)
  • Risperidal M-Tab (Janssen)
  • Risperin
  • Rispolept
  • Rispolin
  • Sequinan
Brand name mixtures Not Available
Categories
  • Antipsychotics
  • Dopamine Antagonists
  • Serotonin Antagonists
  • Antipsychotic Agents
CAS number 106266-06-2
Weight Average: 410.4845
Monoisotopic: 410.211804333
Chemical Formula C23H27FN4O2
InChI Key InChIKey=RAPZEAPATHNIPO-UHFFFAOYSA-N
InChI
InChI=1S/C23H27FN4O2/c1-15-18(23(29)28-10-3-2-4-21(28)25-15)9-13-27-11-7-16(8-12-27)22-19-6-5-17(24)14-20(19)30-26-22/h5-6,14,16H,2-4,7-13H2,1H3
Plain Text
IUPAC Name
3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-2-methyl-4H,6H,7H,8H,9H-pyrido[1,2-a]pyrimidin-4-one
SMILES
CC1=C(CCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C(=O)N2CCCCC2=N1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzoxazoles
Substructures
  • Benzene and Derivatives
  • Isoxazoles
  • Pyrimidines and Derivatives
  • Aliphatic and Aryl Amines
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Oxazoles
  • Imines
  • Cyanamides
  • Aryl Halides
  • Benzoxazoles
  • Piperidines
Pharmacology
Indication For the treatment of schizophrenia in adults and in adolescents, ages 13 to 17, and for the short-term treatment of manic or mixed episodes of bipolar I disorder in children and adolescents ages 10 to 17. May also be used to manage symptoms of inappropriate behavior due to aggression and/or psychosis in patients with severe dementia.
Pharmacodynamics Risperidone is an atypical antipsychotic medication. It is most often used to treat delusional psychosis (including schizophrenia), but risperidone is also used to treat some forms of bipolar disorder and psychotic depression. It also has shown some success in treating symptoms of Asperger's Syndrome and autism. Risperidone is now the most commonly prescribed antipsychotic medication in the United States.
Mechanism of action Blockade of dopaminergic D2 receptors in the limbic system alleviates positive symptoms of schizophrenia such as hallucinations, delusions, and erratic behavior and speech. Blockade of serotonergic 5-HT2 receptors in the mesocortical tract, causes an excess of dopamine and an increase in dopamine transmission, resulting in an increase in dopamine transmission and an elimination of core negative symptoms. Dopamine receptors in the nigrostriatal pathway are not affected by risperidone and extrapyramidal effects are avoided. Like other 5-HT2 antagonists, risperidone also binds at alpha(1)-adrenergic receptors and, to a lesser extent, at histamine H1 and alpha(2)-adrenergic receptors.
Absorption Well absorbed. The absolute oral bioavailability of risperidone is 70% (CV=25%). The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) when compared to a solution.
Volume of distribution
  • 1 to 2 L/kg
Protein binding Risperidone, ~88% bound; 9-hydroxyrisperidone, ~77% bound.
Metabolism

Extensively metabolized by hepatic cytochrome P450 2D6 isozyme to 9-hydroxyrisperidone, which has approximately the same receptor binding affinity as risperidone. Hydroxylation is dependent on debrisoquine 4-hydroxylase and metabolism is sensitive to genetic polymorphisms in debrisoquine 4-hydroxylase. Risperidone also undergoes N-dealkylation to a lesser extent.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2D6 9-hydroxyrisperidone 9-hydroxylation 1.4 39.6
Cytochrome P450 3A7 9-hydroxyrisperidone 9-hydroxylation
Route of elimination Risperidone is extensively metabolized in the liver.In healthy elderly subjects, renal clearance of both risperidone and 9-hydroxyrisperidone was decreased, and elimination half-lives were prolonged compared to young healthy subjects.
Half life 20-24 hours
Clearance Not Available
Toxicity Symptoms of overdose include drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. LD50=82.1mg/kg (orally in mice).
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ortho mcneil janssen pharmaceuticals inc
  • Ortho mcneil janssen pharmaceutical inc
  • Apotex inc richmond hill
  • Aurobindo pharma ltd
  • Dr reddys laboratories ltd
  • Precision dose inc
  • Roxane laboratories inc
  • Teva pharmaceuticals usa inc
  • Wockhardt ltd
  • Par pharmaceutical inc
  • Ranbaxy laboratories inc
  • Sandoz inc
  • Zydus pharmaceuticals usa inc
  • Actavis totowa llc
  • Apotex inc
  • Cadista pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Pliva hrvatska doo
  • Ratiopharm
  • Synthon pharmaceuticals inc
  • Torrent pharmaceuticals ltd
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • West ward pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Injection, powder, for suspension Intramuscular 12.5 mg
Injection, powder, for suspension Intramuscular 25 mg
Injection, powder, for suspension Intramuscular 37.5 mg
Injection, powder, for suspension Intramuscular 50 mg
Solution Oral 1 mg/ml
Tablet, film coated Oral 0.25 mg
Tablet, film coated Oral 0.5 mg
Tablet, film coated Oral 1 mg
Tablet, film coated Oral 2 mg
Tablet, film coated Oral 3 mg
Tablet, film coated Oral 4 mg
Tablet, orally disintegrating Oral 0.5 mg
Tablet, orally disintegrating Oral 1 mg
Tablet, orally disintegrating Oral 2 mg
Tablet, orally disintegrating Oral 3 mg
Tablet, orally disintegrating Oral 4 mg
Prices
Unit description Cost Unit
Risperdal consta 50 mg syr 592.93 USD syringe
Risperdal consta 37.5 mg syr 444.68 USD syringe
Risperdal consta 25 mg syr 296.46 USD syringe
Risperdal 1 mg/ml Solution 30ml Bottle 204.42 USD bottle
Risperdal M-TAB 28 1 mg Dispersible Tablet Box 196.08 USD box
Risperdal M-TAB 28 0.5 mg Dispersible Tablet Bottle 167.82 USD bottle
Risperidone 1 mg/ml Solution 30ml Bottle 158.66 USD bottle
Risperdal consta 12.5 mg syr 148.22 USD syringe
Risperdal m-tab 4 mg odt 18.55 USD tablet
Risperdal 4 mg tablet 16.47 USD tablet
Risperidone m-tab 4 mg odt 15.16 USD tablet
Risperdal m-tab 3 mg odt 13.81 USD tablet
Risperdal 3 mg tablet 11.45 USD tablet
Risperidone m-tab 3 mg odt 11.29 USD tablet
Risperdal m-tab 2 mg odt 10.95 USD tablet
Risperidone 4 mg tablet 9.0 USD tablet
Risperidone m-tab 2 mg odt 8.95 USD tablet
Risperdal 2 mg tablet 6.94 USD tablet
Risperdal m-tab 1 mg odt 6.73 USD tablet
Risperidone 3 mg tablet 6.63 USD tablet
Risperdal 1 mg tablet 6.12 USD tablet
Risperdal m-tab 0.5 mg odt 5.76 USD tablet
Risperidone 2 mg tablet 5.59 USD tablet
Risperidone m-tab 1 mg odt 5.5 USD tablet
Risperidone M-TAB 0.5 mg Dispersible Tablet 4.9 USD dispersible tablet
Risperidone m-tab 0.5 mg odt 4.71 USD tablet
Risperdal M-Tab 4 mg Disintegrating Tablet 4.6 USD tablet
Risperdal 0.25 mg tablet 4.56 USD tablet
Risperidone 0.25 mg odt 4.48 USD tablet
Risperdal 0.5 mg tablet 3.62 USD tablet
Risperdal M-Tab 3 mg Disintegrating Tablet 3.44 USD tablet
Risperidone 1 mg tablet 3.27 USD tablet
Risperidone 0.5 mg tablet 3.03 USD tablet
Apo-Risperidone 4 mg Tablet 2.53 USD tablet
Co Risperidone 4 mg Tablet 2.53 USD tablet
Mylan-Risperidone 4 mg Tablet 2.53 USD tablet
Novo-Risperidone 4 mg Tablet 2.53 USD tablet
Phl-Risperidone 4 mg Tablet 2.53 USD tablet
Pms-Risperidone 4 mg Tablet 2.53 USD tablet
Ran-Risperidone 4 mg Tablet 2.53 USD tablet
Ratio-Risperidone 4 mg Tablet 2.53 USD tablet
Rbx-Risperidone 4 mg Tablet 2.53 USD tablet
Sandoz Risperidone 4 mg Tablet 2.53 USD tablet
Risperdal M-Tab 2 mg Disintegrating Tablet 2.29 USD tablet
Apo-Risperidone 3 mg Tablet 1.9 USD tablet
Co Risperidone 3 mg Tablet 1.9 USD tablet
Mylan-Risperidone 3 mg Tablet 1.9 USD tablet
Novo-Risperidone 3 mg Tablet 1.9 USD tablet
Phl-Risperidone 3 mg Tablet 1.9 USD tablet
Pms-Risperidone 3 mg Tablet 1.9 USD tablet
Ran-Risperidone 3 mg Tablet 1.9 USD tablet
Ratio-Risperidone 3 mg Tablet 1.9 USD tablet
Rbx-Risperidone 3 mg Tablet 1.9 USD tablet
Sandoz Risperidone 3 mg Tablet 1.9 USD tablet
Risperidone 0.25 mg tablet 1.88 USD tablet
Apo-Risperidone 2 mg Tablet 1.26 USD tablet
Co Risperidone 2 mg Tablet 1.26 USD tablet
Mylan-Risperidone 2 mg Tablet 1.26 USD tablet
Novo-Risperidone 2 mg Tablet 1.26 USD tablet
Phl-Risperidone 2 mg Tablet 1.26 USD tablet
Pms-Risperidone 2 mg Tablet 1.26 USD tablet
Ran-Risperidone 2 mg Tablet 1.26 USD tablet
Ratio-Risperidone 2 mg Tablet 1.26 USD tablet
Rbx-Risperidone 2 mg Tablet 1.26 USD tablet
Sandoz Risperidone 2 mg Tablet 1.26 USD tablet
Risperdal M-Tab 1 mg Disintegrating Tablet 1.16 USD tablet
Risperdal M-Tab 0.5 mg Disintegrating Tablet 0.84 USD tablet
Apo-Risperidone 1 mg Tablet 0.63 USD tablet
Co Risperidone 1 mg Tablet 0.63 USD tablet
Mylan-Risperidone 1 mg Tablet 0.63 USD tablet
Novo-Risperidone 1 mg Tablet 0.63 USD tablet
Phl-Risperidone 1 mg Tablet 0.63 USD tablet
Pms-Risperidone 1 mg Tablet 0.63 USD tablet
Ran-Risperidone 1 mg Tablet 0.63 USD tablet
Ratio-Risperidone 1 mg Tablet 0.63 USD tablet
Rbx-Risperidone 1 mg Tablet 0.63 USD tablet
Sandoz Risperidone 1 mg Tablet 0.63 USD tablet
Apo-Risperidone 0.5 mg Tablet 0.46 USD tablet
Co Risperidone 0.5 mg Tablet 0.46 USD tablet
Mylan-Risperidone 0.5 mg Tablet 0.46 USD tablet
Novo-Risperidone 0.5 mg Tablet 0.46 USD tablet
Phl-Risperidone 0.5 mg Tablet 0.46 USD tablet
Pms-Risperidone 0.5 mg Tablet 0.46 USD tablet
Ran-Risperidone 0.5 mg Tablet 0.46 USD tablet
Ratio-Risperidone 0.5 mg Tablet 0.46 USD tablet
Rbx-Risperidone 0.5 mg Tablet 0.46 USD tablet
Sandoz Risperidone 0.5 mg Tablet 0.46 USD tablet
Apo-Risperidone 0.25 mg Tablet 0.27 USD tablet
Co Risperidone 0.25 mg Tablet 0.27 USD tablet
Mylan-Risperidone 0.25 mg Tablet 0.27 USD tablet
Novo-Risperidone 0.25 mg Tablet 0.27 USD tablet
Phl-Risperidone 0.25 mg Tablet 0.27 USD tablet
Pms-Risperidone 0.25 mg Tablet 0.27 USD tablet
Ran-Risperidone 0.25 mg Tablet 0.27 USD tablet
Ratio-Risperidone 0.25 mg Tablet 0.27 USD tablet
Rbx-Risperidone 0.25 mg Tablet 0.27 USD tablet
Sandoz Risperidone 0.25 mg Tablet 0.27 USD tablet
Patents
Country Patent Number Approved Expires
United States 6667061 2000-11-25 2020-11-25
United States 6110921 1993-11-19 2013-11-19
Canada 2406536 2009-12-22 2021-04-19
Canada 2194564 1998-01-27 2015-07-04
Properties
State solid
Melting point 170oC
Experimental Properties
Property Value Source
water solubility 2.8mg/L PhysProp
logP 2.5 PhysProp
Predicted Properties
Property Value Source
water solubility 1.71e-01 g/l ALOGPS
logP 3.27 ALOGPS
logP 2.63 ChemAxon Molconvert
logS -3.38 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 61.94 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 114.55 ChemAxon Molconvert
polarizability 45.27 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Altschuler EL, Kast RE: The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephalopathy. Med Hypotheses. 2005;65(3):585-6. Pubmed
  2. Bostwick JR, Guthrie SK, Ellingrod VL: Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009 Jan;29(1):64-73. Pubmed
  3. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  4. Kemp DE, Canan F, Goldstein BI, McIntyre RS: Long-acting risperidone: a review of its role in the treatment of bipolar disorder. Adv Ther. 2009 Jun;26(6):588-99. Epub 2009 Jun 26. Pubmed
  5. Szarfman A, Tonning JM, Levine JG, Doraiswamy PM: Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006 Jun;26(6):748-58. Pubmed
  6. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. Pubmed
  7. Yamanouchi Y, Iwata N, Suzuki T, Kitajima T, Ikeda M, Ozaki N: Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone. Pharmacogenomics J. 2003;3(6):356-61. Pubmed
External Links
Resource Link
KEGG Drug D00426 Link_out
PubChem Compound 5073 Link_out
PubChem Substance 46505850 Link_out
ChemSpider 4895 Link_out
ChEBI 8871 Link_out
ChEMBL 8871 Link_out
Therapeutic Targets Database DAP000003 Link_out
PharmGKB PA451257 Link_out
Drug Product Database 2247705 Link_out
RxList http://www.rxlist.com/cgi/generic/risperid.htm Link_out
Drugs.com http://www.drugs.com/risperidone.html Link_out
PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=ris1382.html&contentName=Risperdal&contentId=667 Link_out
Wikipedia http://en.wikipedia.org/wiki/Risperidone Link_out
ATC Codes
  • N05AX08
AHFS Codes
  • 28:16.08.04
PDB Entries Not Available
FDA label show (2.5 MB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  2. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. Pubmed
  3. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed
  4. Uchida S, Kato Y, Hirano K, Kagawa Y, Yamada S: Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine. Life Sci. 2007 Apr 3;80(17):1635-40. Epub 2007 Jan 27. Pubmed

2. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Catafau AM, Corripio I, Perez V, Martin JC, Schotte A, Carrio I, Alvarez E: Dopamine D2 receptor occupancy by risperidone: implications for the timing and magnitude of clinical response. Psychiatry Res. 2006 Dec 1;148(2-3):175-83. Epub 2006 Oct 23. Pubmed
  2. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  3. Lane HY, Lee CC, Chang YC, Lu CT, Huang CH, Chang WH: Effects of dopamine D2 receptor Ser311Cys polymorphism and clinical factors on risperidone efficacy for positive and negative symptoms and social function. Int J Neuropsychopharmacol. 2004 Dec;7(4):461-70. Epub 2004 May 12. Pubmed
  4. Naiker DV, Catts SV, Catts VS, Bedi KS, Bryan-Lluka LJ: Dose determination of haloperidol, risperidone and olanzapine using an in vivo dopamine D2-receptor occupancy method in the rat. Eur J Pharmacol. 2006 Jul 1;540(1-3):87-90. Epub 2006 May 11. Pubmed
  5. Remington G, Mamo D, Labelle A, Reiss J, Shammi C, Mannaert E, Mann S, Kapur S: A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone. Am J Psychiatry. 2006 Mar;163(3):396-401. Pubmed
  6. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. D(3) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P35462 Link_out
Gene: DRD3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. Pubmed
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. Pubmed

4. D(4) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out
Gene: DRD4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. Pubmed
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. Pubmed

5. Alpha-1A adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Eltze M: In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha 1-adrenoceptors. Eur J Pharmacol. 1996 Jan 4;295(1):69-73. Pubmed
  2. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  3. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. Pubmed
  4. Nourian Z, Mow T, Muftic D, Burek S, Pedersen ML, Matz J, Mulvany MJ: Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of alpha1-adrenoceptor function. Psychopharmacology (Berl). 2008 Jul;199(1):15-27. Epub 2008 Jun 10. Pubmed
  5. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed
  6. Sleight AJ, Koek W, Bigg DC: Binding of antipsychotic drugs at alpha 1A- and alpha 1B-adrenoceptors: risperidone is selective for the alpha 1B-adrenoceptors. Eur J Pharmacol. 1993 Jul 20;238(2-3):407-10. Pubmed

6. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Eltze M: In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha 1-adrenoceptors. Eur J Pharmacol. 1996 Jan 4;295(1):69-73. Pubmed
  3. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  4. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. Pubmed
  5. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed
  6. Sleight AJ, Koek W, Bigg DC: Binding of antipsychotic drugs at alpha 1A- and alpha 1B-adrenoceptors: risperidone is selective for the alpha 1B-adrenoceptors. Eur J Pharmacol. 1993 Jul 20;238(2-3):407-10. Pubmed

7. 5-hydroxytryptamine 1D receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28221 Link_out
Gene: HTR1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed

8. Histamine H1 receptor

Pharmacological action: unknown
Actions: antagonist

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. Pubmed
  2. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed
  3. Schreiber S, Backer MM, Weizman R, Pick CG: Augmentation of opioid induced antinociception by the atypical antipsychotic drug risperidone in mice. Neurosci Lett. 1997 May 30;228(1):25-8. Pubmed

9. Alpha-2A adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  2. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed

10. Alpha-2B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist, agonist

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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out
Gene: ADRA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  2. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed

11. Alpha-2C adrenergic receptor

Pharmacological action: unknown
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out
Gene: ADRA2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
  2. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed

12. 5-hydroxytryptamine 2C receptor

Pharmacological action: unknown
Actions: antagonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed
  2. Canton H, Verriele L, Millan MJ: Competitive antagonism of serotonin (5-HT)2C and 5-HT2A receptor-mediated phosphoinositide (PI) turnover by clozapine in the rat: a comparison to other antipsychotics. Neurosci Lett. 1994 Nov 7;181(1-2):65-8. Pubmed

13. 5-hydroxytryptamine 1A receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. Pubmed

14. D(1A) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. Pubmed
  2. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fang J, Bourin M, Baker GB: Metabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4. Naunyn Schmiedebergs Arch Pharmacol. 1999 Feb;359(2):147-51. Pubmed
  2. Hendset M, Molden E, Refsum H, Hermann M: Impact of CYP2D6 genotype on steady-state serum concentrations of risperidone and 9-hydroxyrisperidone in patients using long-acting injectable risperidone. J Clin Psychopharmacol. 2009 Dec;29(6):537-41. Pubmed
  3. Zhou SF: Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmacokinet. 2009;48(12):761-804. Pubmed
  4. Zhou SF: Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723. Pubmed
  5. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  6. Effexor XR Product Reference Source
  7. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  8. Yasui-Furukori N, Hidestrand M, Spina E, Facciola G, Scordo MG, Tybring G: Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes. Drug Metab Dispos. 2001 Oct;29(10):1263-8. Pubmed

2. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fang J, Bourin M, Baker GB: Metabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4. Naunyn Schmiedebergs Arch Pharmacol. 1999 Feb;359(2):147-51. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A5

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A7

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
Transporters

1. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Boulton DW, DeVane CL, Liston HL, Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 2002 May 31;71(2):163-9. Pubmed
  2. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.