Owen R T
Crewe, Cheshire, UK.
Drugs Today (Barc). 2011 Nov;47(11):807-16. doi: 10.1358/dot.2011.47.11.1708832.
Lurasidone is a novel benzoisothiazol antipsychotic that has recently been approved for the treatment of schizophrenia in the U.S. Like many other second-generation antipsychotics, it has a high affinity for dopamine D(2) and serotonin 5-HT(2A) receptors as well as a high affinity for 5-HT(7) receptors. It has negligible affinity for α(1)-adrenoceptors, histamine H(1) receptors or muscarinic acetylcholine M(1) receptors. It has demonstrated efficacy in short-term trials versus placebo, two of which included an active comparator (olanzapine, quetiapine) assay arm. A short-term, head-to-head trial of lurasidone versus ziprasidone in chronic stable schizophrenia was also conducted. A long-term, 12-month risperidone-controlled study and open-label studies primarily investigated the safety and tolerability of lurasidone. Limited evidence of procognitive and antidepressant effects was seen although these need further corroboration. The incidence of extrapyramidal symptoms (excluding akathisia/restlessness) was greater with lurasidone (14.7%) than placebo (5.1%). Akathisia and somnolence were dose-related adverse events. Lurasidone appears to have relatively little effect on weight, plasma glucose or lipids to date. No evidence of QTc prolongation was seen and orthostatic hypotension was uncommon. Raised prolactin levels in short-term studies were dose-dependent, greater in females and occurred overall in 3.7 and 0.7% of lurasidone and placebo recipients, respectively.
鲁拉西酮是一种新型苯并异噻唑类抗精神病药物,最近在美国被批准用于治疗精神分裂症。与许多其他第二代抗精神病药物一样,它对多巴胺D(2)和5-羟色胺5-HT(2A)受体具有高亲和力,对5-HT(7)受体也具有高亲和力。它对α(1)-肾上腺素能受体、组胺H(1)受体或毒蕈碱型乙酰胆碱M(1)受体的亲和力可忽略不计。在与安慰剂对照的短期试验中已证明其有效性,其中两项试验包括活性对照药(奥氮平、喹硫平)测定组。还进行了一项鲁拉西酮与齐拉西酮治疗慢性稳定型精神分裂症的短期、直接比较试验。一项为期12个月的、以利培酮为对照的长期研究和开放标签研究主要考察了鲁拉西酮的安全性和耐受性。虽然需要进一步证实,但已观察到有限的促认知和抗抑郁作用证据。鲁拉西酮组锥体外系症状(不包括静坐不能/烦躁不安)的发生率(14.7%)高于安慰剂组(5.1%)。静坐不能和嗜睡是与剂量相关的不良事件。迄今为止,鲁拉西酮似乎对体重、血糖或血脂影响相对较小。未观察到QTc延长的证据,直立性低血压也不常见。短期研究中催乳素水平升高呈剂量依赖性,女性中更常见,鲁拉西酮组和安慰剂组总体发生率分别为3.7%和0.7%。