Clozapine

• 产品号: DB00363
• CAS号: 5786-21-0
• 分子式: C18H19ClN4
• 分子量: 326.82326

产品别名

• 标题: Clozapine
• IUPAC标准名: 6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
• IUPAC传统名: 6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
• 商标名: Iprox; Clozaril; Asaleptin; Fazaclo ODT; Leponex; Lepotex
• 别名: Clozapin

产品登记号

• CAS号: 5786-21-0
• PubChem SID: 46506474
• PubChem CID: 2818

产品性质

• 疏水性(logP): 2.7
• 溶解度: 11.8 mg/L

产品详细信息

详细说明 (English)

• Drug Groups: approved
• Description: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [PubChem]
• Indication: For use in patients with treatment-resistant schizophrenia.
• Pharmacology: Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT₂), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT₂ with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
• Toxicity: Clozapine carries a black-box warning for agranulocytosis.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Rapid and almost complete
• Half Life: 8 hours (range 4-12 hours)
• Protein Binding: 97% (bound to serum proteins)
• Elimination: Approximately 50% of the administered dose is excreted in the urine and 30% in the feces.
• References: Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA: Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993 Jul 15;329(3):162-7. [Pubmed] ; Vaddadi KS, Soosai E, Vaddadi G: Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol. 2003 Mar;55(3):307-9. [Pubmed] ; Naheed M, Green B: Focus on clozapine. Curr Med Res Opin. 2001;17(3):223-9. [Pubmed] ; Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW: Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999 Jan;60(1):36-40. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

参考文献

• Naheed M, Green B: Focus on clozapine. Curr Med Res Opin. 2001;17(3):223-9. Pubmed
• Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA: Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993 Jul 15;329(3):162-7. Pubmed
• Vaddadi KS, Soosai E, Vaddadi G: Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol. 2003 Mar;55(3):307-9. Pubmed
• Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW: Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999 Jan;60(1):36-40. Pubmed