Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.
Department of Neuropsychiatry, Horikoshi Psychosomatic Clinic, Fukushima, Japan.
Drug Des Devel Ther. 2023 Sep 28;17:3023-3031. doi: 10.2147/DDDT.S366769. eCollection 2023.
This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D, 5-hydroxytryptamine (5-HT), and 5-HT receptors and a partial agonistic effect on the 5-HT receptor with low affinities for muscarinic M, histamine H, and a adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT and 5-HT receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.
这篇综述旨在提供一个全面的文献综述，介绍鲁拉西酮的药物设计、开发和治疗精神分裂症的治疗方法。鲁拉西酮对多巴胺 D、5-羟色胺（5-HT）和 5-HT 受体具有拮抗作用，对 5-HT 受体具有部分激动作用，对毒蕈碱 M、组胺 H 和肾上腺素能受体的亲和力较低。鲁拉西酮的受体结合谱被认为与较少的副作用有关，如抗胆碱能作用、脂质异常、高血糖和体重增加。行为药理学研究表明，鲁拉西酮具有抗焦虑和抗抑郁作用，并改善认知功能，这与 5-HT 和 5-HT 受体的调节有关。使用 PubMed 进行文献检索，以查找关于疗效和安全性的随机对照试验和最近的荟萃分析的已发表研究，特别是鲁拉西酮在精神分裂症中的代谢副作用。在短期研究中，随机安慰剂对照试验和荟萃分析的结果表明，鲁拉西酮在改善急性精神分裂症患者的总精神病学、阳性症状、阴性症状和一般精神病学方面优于安慰剂。关于安全性，鲁拉西酮的代谢副作用最小，被认为是代谢副作用最良性的药物之一。长期试验表明，鲁拉西酮具有预防复发的作用，对体重增加和其他代谢副作用的影响最小。此外，鲁拉西酮可改善精神分裂症患者的认知和功能表现，特别是在长期治疗中。精神分裂症患者需要长期服用抗精神病药物预防复发；因此，最大限度地减少体重增加和其他副作用至关重要。鲁拉西酮适合作为急性期的一线抗精神病药物之一，在维持期应考虑转换策略，以平衡疗效和不良反应，在精神分裂症的长期病程中取得良好的效果。
