Courtesy Assistant Professor, Department of Psychiatry, University of Florida, and CEO and Medical Director, Florida Clinical Research Center, LLC, 3914 SR 64 E, Bradenton, FL 34208, USA.
Expert Rev Neurother. 2009 Dec;9(12):1727-41. doi: 10.1002/pmic.200800563.
Schizophrenia is a debilitating condition associated with high morbidity and mortality. While currently available atypical antipsychotic agents have significantly advanced the treatment of schizophrenia, there is still a great unmet need for new, effective and better-tolerated therapies. Iloperidone, a D(2)/5-HT(2) receptor antagonist, has been recently approved by the US FDA for the acute treatment of schizophrenia in adults. Iloperidone has been shown to be effective in the treatment of schizophrenia in four short-term (4-6 weeks) and three long-term (52 weeks) studies with over 3000 patients exposed to treatment. Results also indicated a reassuring safety profile, particularly regarding extrapyramidal symptoms, akathisia and prolactin elevation, with a modest effect on weight gain and no medically important changes in cholesterol, triglycerides and glucose. As other antipsychotics, iloperidone has been shown to prolong the QTc interval. Since none of the current therapies work for every patient, a pharmacogenetic approach was used to identify genetic markers associated with increased response to iloperidone, suggesting a personalized therapeutic option for this drug. In addition, a long-term 4-week injectable formulation is being developed that may assist with patient compliance. Key development findings for iloperidone are presented here.
精神分裂症是一种使人虚弱的疾病,与高发病率和死亡率相关。尽管目前可用的非典型抗精神病药物已极大地推进了精神分裂症的治疗,但对于新的、有效和耐受性更好的治疗方法仍有巨大的未满足需求。依洛哌酮是一种 D2/5-HT2 受体拮抗剂,最近已被美国 FDA 批准用于成人精神分裂症的急性治疗。四项短期(4-6 周)和三项长期(52 周)研究共纳入 3000 多名接受治疗的患者,结果表明依洛哌酮对精神分裂症的治疗有效。结果还表明其具有可靠的安全性特征,尤其是在锥体外系症状、静坐不能和催乳素升高方面,对体重增加的影响较小,对胆固醇、甘油三酯和葡萄糖无重要的医学影响。与其他抗精神病药物一样,依洛哌酮也被证明会延长 QTc 间期。由于目前没有一种治疗方法对每个患者都有效,因此采用了药物遗传学方法来确定与依洛哌酮反应增加相关的遗传标记,这表明该药物具有个性化治疗的选择。此外,还正在开发一种长效 4 周注射制剂,以帮助提高患者的依从性。本文介绍了依洛哌酮的关键开发发现。