Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Rev Neurosci. 2018 Mar 28;29(3):333-345. doi: 10.1515/revneuro-2017-0043.
Accumulating experimental data suggests a number of successful drug targets against epilepsy which eventually failed in the clinical setup. Mammalian target of rapamycin inhibitors, multi-drug resistance transporter inhibitors, cyclo-oxygenase-2 inhibitors, statins, etc. are the most promising and well studied among them. Drugs aiming at these targets produced beneficial response in most of the in vitro and in vivo seizure models. However, in certain situations, they have produced differential rather controversial results. Their effects varied with the seizure model, species, time and route of administration, different drugs from the same class, etc. This review emphasises on such drugs which presented with variability in their beneficial effects against seizures and epilepsy. This review critically summarises the preclinical evidence of these targets in the context of seizures and the probable reasons for their variability and clinical failures.
积累的实验数据表明，许多针对癫痫的有效药物靶点最终在临床环境中失败。雷帕霉素靶蛋白抑制剂、多药耐药转运体抑制剂、环氧化酶-2 抑制剂、他汀类药物等是其中最有前途和研究最充分的药物。针对这些靶点的药物在大多数体外和体内癫痫发作模型中产生了有益的反应。然而，在某些情况下，它们产生了不同的、有争议的结果。它们的作用因癫痫发作模型、物种、时间和给药途径、同一类别的不同药物等因素而有所不同。本综述强调了这些药物在对抗癫痫发作方面的有益效果存在差异。本综述批判性地总结了这些靶点在癫痫发作背景下的临床前证据，以及它们产生差异和临床失败的可能原因。
