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

• ChemBase ID: 615
• Molecular Formular: C23H27FN4O2
• Molecular Mass: 410.4844832
• Monoisotopic Mass: 410.21180434
• SMILES: Fc1cc2onc(C3CCN(CC3)CCc3c(=O)n4CCCCc4nc3C)c2cc1
• Canonical SMILES: Fc1ccc2c(c1)onc2C1CCN(CC1)CCc1c(C)nc2n(c1=O)CCCC2
• 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
• InChIKey: RAPZEAPATHNIPO-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• 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
• IUPAC Traditional name: risperidone; 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
• Brand Name: Risperdal; Risperdal Consta; Risperdal M-Tab; Risperidal M-Tab; Risperin; Rispolept; Rispolin; Sequinan
• Synonyms: R 64,766; Risperidone; Risperidona [Spanish]; Risperidonum [Latin]; risperidone; risperdone; Risperidone; 3-[2-4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one; Apexidone; Psychodal; R 64766; Rispadal; Risperdal Consta; Risperidal; Spiron; Belivon; Rispolin; 3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido [1,2-a] pyrimidin-4-one; R 64 766; Risperdal; Risperidone(Risperdal)

Database IDs

• CAS Number: 106266-06-2
• MDL Number: MFCD00274576
• PubChem SID: 46505850; 160964078
• PubChem CID: 5073

CALCULATED PROPERTIES

JChem

• LogD (pH = 7.4): 1.2491776
• Log P: 2.6276212
• Molar Refractivity: 114.5492 cm^3
• Polarizability: 43.907574 Å^3
• Polar Surface Area: 61.94 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true
• H Acceptors: 4
• H Donor: 0
• LogD (pH = 5.5): -0.43775237

ALOGPS 2.1

• Log P: 3.27
• LOG S: -3.38
• Solubility (Water): 1.71e-01 g/l

PROPERTIES

Physical Property

• Solubility: 2.8mg/L; Chloroform; DMSO: ≥5 mg/mL; Methanol
• Apperance: Crystalline Solid; white to off-white powder
• Melting Point: 170°C; 170-172°C
• Hydrophobicity(logP): 2.5

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• RTECS: UV1164800
• European Hazard Symbols: Toxic (T); Harmful (Xn)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3; III
• Australian Hazchem: 2X
• Risk Statements: 25; R:22
• Safety Statements: 28-36-45; S:36/37/39
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154
• GHS Pictograms: GHS06
• GHS Signal Word: Danger
• GHS Hazard statements: H301
• GHS Precautionary statements: P301 + P310
• Personal Protective Equipment: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• Storage Temperature: room temp

Pharmacology Properties

• Mechanism of Action: 5-HT 2 and dopamine-D 2 receptor antagonist; Also adrenergic receptor activity

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: Free Base
• Application(s): Antipsychotic agent; Used for the treatment of schizophrenia and bipolar disorder
• Empirical Formula (Hill Notation): C23H27FN4O2

DETAILS

MP Biomedicals - 02193714

Both a D₂ dopamine and 5-HT₂ serotonin receptor antagonist.

DrugBank - DB00734

• Drug Groups: approved; investigational
• 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.
• 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.
• Pharmacology: 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.
• 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
• Biotransformation: 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.
• 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.
• Half Life: 20-24 hours
• Protein Binding: Risperidone, ~88% bound; 9-hydroxyrisperidone, ~77% bound.
• 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.
• Distribution: * 1 to 2 L/kg
• References: 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] ; Bostwick JR, Guthrie SK, Ellingrod VL: Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009 Jan;29(1):64-73. [Pubmed] ; Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. [Pubmed] ; 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] ; Szarfman A, Tonning JM, Levine JG, Doraiswamy PM: Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006 Jun;26(6):748-58. [Pubmed] ; 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] ; 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: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1615

Research Area: Neurological Disease
Biological Activity:
Risperidone(Risperdal) is an atypical antipsychotic used to treat schizophrenia (including adolescent schizophrenia), schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in children with autism. This drug has more pronounced serotonin antagonism than dopamine antagonism. It has high affinity for D2 dopaminergic receptors. It has actions at several 5-HT (serotonin) receptor subtypes. [1]

Sigma Aldrich - R3030

Biochem/physiol Actions
Risperidone is an antipsychotic; serotonin-dopamine antagonist.

Toronto Research Chemicals - R525000

A combined serotonin (5-HT2) and dopamine (D2) receptor antagonist.

REFERENCES

• 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
• 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
• Bostwick JR, Guthrie SK, Ellingrod VL: Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009 Jan;29(1):64-73. Pubmed
• Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. Pubmed
• 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
• Szarfman A, Tonning JM, Levine JG, Doraiswamy PM: Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006 Jun;26(6):748-58. Pubmed
• 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
• http://en.wikipedia.org/wiki/Risperidone
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