Department of Psychiatry, University of California, San Diego, CA 92161, USA.
Expert Opin Investig Drugs. 2009 Nov;18(11):1715-26. doi: 10.1517/13543780903286388.
Lurasidone is a novel psychotropic agent in development for the treatment of schizophrenia and bipolar disorder.
This paper describes the development of lurasidone, including its receptor binding affinities, pharmacokinetics, CNS activity in rodent models and results of early clinical efficacy and safety studies in humans.
The available literature on lurasidone was reviewed, including abstracts from medical congresses supplemented by data on file with the sponsor.
RESULTS/CONCLUSIONS: Lurasidone has a high affinity for dopamine D(2) and serotonin 5-HT(2A) receptors as well as for receptors implicated in enhancement of cognitive function (e.g., 5-HT(7,) 5-HT(1A), alpha(2c)). Lurasidone has no affinity for muscarinic M(1) and histamine H(1) receptors and minimal affinity for alpha(1) adrenoceptors, dopamine D(1) and D(3) receptors, serotonin 5-HT(2C) receptors and alpha(2A) adrenoceptors. Phase II efficacy data indicate that lurasidone doses from 40 to 120 mg/day are effective in the treatment of schizophrenia, with positive symptom reduction exceeding that for negative symptoms, as seen with other antipsychotics. Preclinical data indicate that lurasidone reverses MK-801 induced learning and memory impairment in rodents, and active comparator data from a Phase Ib study of lurasidone 120 mg/day versus ziprasidone 160 mg/day also found a signal for effects on cognition. Phase II studies suggest that lurasidone has no significant QTc prolongation and a benign metabolic profile.
鲁拉西酮是一种新型精神药物，正在开发用于治疗精神分裂症和双相情感障碍。
本文描述了鲁拉西酮的开发情况，包括其受体结合亲和力、药代动力学、在啮齿动物模型中的中枢神经系统活性以及早期临床疗效和安全性研究的结果。
综述了鲁拉西酮的现有文献，包括医学大会摘要，并辅以赞助商提供的文件中的数据。
结果/结论：鲁拉西酮对多巴胺 D2 和 5-羟色胺 5-HT2A 受体以及与增强认知功能有关的受体（如 5-HT7、5-HT1A、α2c）具有高亲和力。鲁拉西酮对毒蕈碱 M1 和组胺 H1 受体没有亲和力，对 α1 肾上腺素受体、多巴胺 D1 和 D3 受体、5-羟色胺 5-HT2C 受体和 α2A 肾上腺素受体的亲和力也很小。II 期疗效数据表明，鲁拉西酮剂量为 40 至 120mg/天对精神分裂症有效，阳性症状的减轻超过阴性症状，与其他抗精神病药物相似。临床前数据表明，鲁拉西酮可逆转 MK-801 诱导的啮齿动物学习和记忆障碍，而鲁拉西酮 120mg/天与齐拉西酮 160mg/天的 Ib 期活性对照研究也发现了对认知有影响的信号。II 期研究表明，鲁拉西酮无明显的 QTc 延长和良性代谢特征。
