122883-93-6

往烧瓶中加入25ml水和6.91g碳酸钠，搅拌使成溶液。加入4.68g5-(2-氯乙基)-6-氯-1,2-二氢-2H-吲哚-2-酮和4.90g3-哌嗪基-1,2-苯并异噻唑盐酸盐，在100℃回流14h，取样进行HPLC测试，继续回流2h。然后冷却至20℃，搅拌1h。过滤收集产物，尽量抽干，然后将其和25ml异丙醇一起搅拌少许，过滤收集产物，以小量异丙醇洗，真空干燥。得7.29g产物，收率92.1%，纯度98.6%。

Ziprasidone HCl 是一类有效的dopamine 和 serotonin (5-HT) receptor的拮抗剂，用于精神分裂症以及双向性障碍的治疗。

Ziprasidone has high affinity for human 5-HT receptors and for human dopamine D(2) receptors. Ziprasidone is a 5-HT(1A) receptor agonist and an antagonist at 5-HT(2A), 5-HT(2C) and 5-HT(1B/1D) receptors. Ziprasidone inhibits neuronal uptake of 5-HT and norepinephrine comparable to the antidepressant imipramine. Ziprasidone blocks wild-type hERG current in a voltage- and concentration-dependent manner with IC(50) of 120nM in stably transfected HEK-293 cells. Ziprasidone shows minimal tonic block of hERG current estimated during a depolarizing voltage (-20 or +30mV) or evaluated by the envelope of tails test (+30mV). Ziprasidone significantly increases the time constant of the slow component of hERG current deactivation (at -50mV).

Ziprasidone exhibits less potent block of wild-type hERG current with IC(50) of 2.8 mM in Xenopus oocytes. Ziprasidone suppresses the significant increases in food intake produced by olanzapine, indicating that it has an intrinsic protective mechanism against drug-induced increases in food intake in rats. Ziprasidone results in a notable increase in NGF and ChAT immunoreactivity in the dentate gyrus (DG), CA1, and CA3 areas of the hippocampus of rats. Ziprasidone dose-dependently slows raphe unit activity (ED50 = 300 mg/kg i.v.) as does the atypical antipsychotics clozapine (ED50 = 250 mg/kg i.v.) and olanzapine (ED50 = 1000 mg/kg i.v.) in anesthetized rats.

Ziprasidone HCl (CP-88059) 是一类有效的dopamine 和 serotonin (5-HT) receptor的拮抗剂，用于精神分裂症以及双向性障碍的治疗。

Target	Value
5-HT receptor
Dopamine receptor

Ziprasidone对人5-HT受体和人多巴胺D(2)受体具有高亲和力。Ziprasidone是一种5-HT(1A)受体激动剂，也是一种5-HT(2A)，5-HT(2C)和5-HT(1B/1D)受体拮抗剂。Ziprasidone抑制5-HT和去甲肾上腺素的神经元摄取，作用与抗抑郁药imipramine相当。 在稳定转染的HEK-293细胞中，Ziprasidone以电压和浓度依赖的方式阻断野生型hERG电流，IC(50) 为120nM。在去极化电压(-20或+30mV)期间估计，或通过悬尾实验(+30mV)的包膜评估，Ziprasidone表现出最小限度的hERG电流强直阻断。Ziprasidone显著增加hERG电流去活化作用(-50mV)慢反应的时间常数。

Ziprasidone对野生型hERG电流表现出较低的阻断作用，在Xenopus卵母细胞中IC(50)为2.8 mM。 在大鼠体内，Ziprasidone抑制olanzapine产生的食物摄取显著增加，表明其对药物诱导的食物摄取增加具有固有的保护机制。 Ziprasidone导致大鼠海马体的齿状回(DG)，CA1，和CA3区域NGF和ChAT免疫反应性显著增加。 在麻醉的大鼠体内，如非典型抗精神病药clozapine (ED50 = 250 mg/kg i.v.)和olanzapine (ED50 = 1000 mg/kg i.v.)，Ziprasidone也能够剂量依赖性减慢中缝单元活性(ED50 = 300 mg/kg i.v.)。