Department of Chemical Engineering and Biotechnology , University of Cambridge , Cambridge CB3 0AS , U.K.
ACS Chem Neurosci. 2019 Jan 16;10(1):58-78. doi: 10.1021/acschemneuro.8b00205. Epub 2018 Jul 18.
There is a paucity of efficacious novel drugs to address high rates of treatment resistance and refractory symptoms in schizophrenia. The identification of novel therapeutic indications for approved drugs-drug repurposing-has the potential to expedite clinical trials and reduce the costly risk of failure which currently limits central nervous system drug discovery efforts. In the present Review we discuss the historical role of drug repurposing in schizophrenia drug discovery and review the main classes of repurposing candidates currently in clinical trials for schizophrenia in terms of their therapeutic rationale, mechanisms of action, and preliminary results from clinical trials. Subsequently we outline the challenges and limitations which face the clinical repurposing pipeline and how novel technologies might serve to address these.
针对精神分裂症治疗抵抗和难治性症状的高发生率，目前有效的新型药物十分匮乏。而重新定位已批准药物的新治疗适应症（药物再利用）有可能加快临床试验的速度，并降低目前限制中枢神经系统药物发现工作的昂贵失败风险。在本综述中，我们讨论了药物再利用在精神分裂症药物发现中的历史作用，并根据其治疗原理、作用机制和临床试验的初步结果，回顾了目前正在临床试验中用于治疗精神分裂症的主要再利用候选药物类别。随后，我们概述了临床再利用管道所面临的挑战和限制，以及新型技术如何解决这些问题。
