产品描述

Ziprasidone hydrochloride monohydrate (CP 88059 hydrochloride monohydrate) is a combined 5-HT (serotonin) and dopamine receptor antagonist which exhibits potent effects of antipsychotic activity. Target: 5-HT receptor; Dopamine receptor Ziprasidone hydrochloride monohydrate is the salt form of ziprasidone, which possesses an in vitro 5-HT2A/dopamine D2 receptor affinity ratio higher than any clinically available antipsychotic agent. In vivo, Ziprasidone hydrochloride monohydrate antagonizes 5-HT2A receptor-induced head twitch with 6-fold higher potency than for blockade of d-amphetamine-induced hyperactivity, a measure of central dopamine D2 receptor antagonism. Ziprasidone hydrochloride monohydrate also has high affinity for the 5-HT1A, 5-HT1D and 5-HT2C receptor subtypes, which may further enhance its therapeutic potential [1]. Ziprasidone hydrochloride monohydrate sulfoxide and sulfone were the major metabolites in human serum. The affinities of the sulfoxide and sulfone metabolites for 5-HT2 and D2 receptors are low with respect to Ziprasidone hydrochloride monohydrate, and are thus unlikely to contribute to its antipsychotic effects [2]. Ziprasidone hydrochloride monohydrate was associated with significant differential adverse effects relative to placebo in BPM, BPD, and schizophrenia with no significant difference in weight gain in all 3 groups. Self-reported somnolence was increased across the 3 conditions. Subjects with BPM were more vulnerable to EPS than those with BPD or schizophrenia [3]. Clinical indications: Bipolar I disorder; Bipolar disorder; Mania; Schizophrenia FDA Approved Date: February 2001

靶点（IC50 & Targe）

5-HT transporter,53nM(Ki)

5-HT1A,12Nm(Ki)

5-HT1B,4.0nM(Ki)

5-HT1D,2.3nM(Ki)

5-HT2A,0.6nM(Ki)

5-HT2C,13nM(Ki)

5-HT6,61nM(Ki)

5-HT7,6nM(Ki)

D1,30nM(Ki)

D2,6.8nM(Ki)

D3,7.2nM(Ki)

H1 receptor,63nM(Ki)

norepinephrine transporter (NET),48nM(Ki)

α1A-adrenergic receptor,18nM(Ki)

α2A-adrenergic receptor,160nM(Ki)

参考文献

[1]. Papakostas GI, Petersen TJ, Nierenberg AA, et al. Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder. The Journal of Clinical Psychiatry. 2004, 65(2):217-221.

[2]. Paul E. Keck, Marcio Versiani, Steven Potkin, et al. Ziprasidone in the Treatment of Acute Bipolar Mania: A Three-Week, Placebo-Controlled, Double-Blind, Randomized Trial. Am J Psychiatry 2003;160:741-748.

[3]. Glen L. Stimmel, Mary A. Gutierrez, Vivian Lee. Ziprasidone: An atypical antipsychotic drug for the treatment of schizophrenia. Clinical Therapeutics, 2002, 24(1):21-37.

[4]. Anne W Schmidt, Lorraine A Lebel, Harry R Howard Jr. et al. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. European Journal of Pharmacology. 2001,425(3):197-201.

[5]. Ziprasidone