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药品详细

Risperidone(利培酮)

化学结构式图
中文名
利培酮
英文名
Risperidone
分子式
C23H27FN4O2
化学名
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
分子量
Average: 410.4845
Monoisotopic: 410.211804333
CAS号
106266-06-2
ATC分类
N05A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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.

生产厂家
  • Actavis totowa llc
  • Apotex inc
  • Apotex inc richmond hill
  • Aurobindo pharma ltd
  • Cadista pharmaceuticals inc
  • Dr reddys laboratories ltd
  • Mylan pharmaceuticals inc
  • Ortho mcneil janssen pharmaceutical inc
  • Ortho mcneil janssen pharmaceuticals inc
  • Par pharmaceutical inc
  • Pliva hrvatska doo
  • Precision dose inc
  • Ranbaxy laboratories inc
  • Ratiopharm
  • Roxane laboratories inc
  • Sandoz inc
  • Synthon pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • West ward pharmaceuticals corp
  • Wockhardt ltd
  • Zydus pharmaceuticals usa inc
封装厂家
参考
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
剂型
规格
化合物类型
Type small molecule
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
适应症
药理
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Risperidone
9-hydroxyrisperidone Details
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
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 170 °C PhysProp
water solubility 2.8mg/L Not Available
logP 2.5 Not Available
Predicted Properties
Property Value Source
water solubility 1.71e-01 g/l ALOGPS
logP 3.27 ALOGPS
logP 2.63 ChemAxon
logS -3.4 ALOGPS
pKa (strongest basic) 8.76 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 61.94 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 114.55 ChemAxon
polarizability 45.27 ChemAxon
药物相互作用
Drug Interaction
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Carbamazepine Decreases the effect of risperidone
Donepezil Possible antagonism of action
Fluoxetine The SSRI, fluoxetine, increases the effect and toxicity of risperidone.
Galantamine Possible antagonism of action
Indinavir Increased risk of extrapyramidal symptoms
Itraconazole Increases the level of risperidone
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Paliperidone Paliperidone is the active metabolite of risperidone, 9-OH-risperidone. Concomitant therapy may increase the adverse effects of paliperidone due to additive paliperidone exposure. Consider alternate therapy.
Paroxetine The SSRI, paroxetine, increases the effect and toxicity of risperidone.
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Risperidone, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Terbinafine Terbinafine may reduce the metabolism and clearance of Risperidone. Consider alternate therapy or monitor for therapeutic/adverse effects of Risperidone if Terbinafine is initiated, discontinued or dose changed.
Tetrabenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimethobenzamide Trimethobenzamide and Risperidone, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine Triprolidine and Risperidone, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Trospium Trospium and Risperidone, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
食物相互作用
Not Available

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