Green A Richard, Shuaib Ashfaq
Global Discovery CNS & Pain Control, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, LE11 5RH, UK.
Drug Discov Today. 2006 Aug;11(15-16):681-93. doi: 10.1016/j.drudis.2006.06.001.
Acute ischaemic stroke is a major health problem with no effective treatments apart from the thrombolytic recombinant tissue plasminogen activator (rt-PA), which must be given within 3h of stroke onset. However, rt-PA increases the risk of symptomatic intracranial haemorrhage and is administered to <5% of stroke patients. New perfusion-enhancing compounds are in development but the risk:benefit ratio remains to be determined. Many neuroprotective drugs have been studied but all those that reached clinical development have failed to demonstrate efficacy. However, adherence to recently published guidelines on preclinical development has resulted in one novel compound (NXY-059) demonstrating efficacy in a Phase III trial, providing encouragement for the validity of the concept of neuroprotection. There are a variety of new neuroprotective compounds in the early stages of investigation and some could prove clinically effective, provided appropriate preclinical development guidelines are observed.
急性缺血性中风是一个重大的健康问题，除了溶栓重组组织型纤溶酶原激活剂（rt-PA）外没有有效的治疗方法，rt-PA必须在中风发作后3小时内给药。然而，rt-PA会增加有症状颅内出血的风险，且仅用于不到5%的中风患者。新的灌注增强化合物正在研发中，但风险效益比仍有待确定。许多神经保护药物已经过研究，但所有进入临床开发阶段的药物都未能证明其疗效。然而，遵循最近发布的临床前开发指南，有一种新型化合物（NXY-059）在III期试验中显示出疗效，这为神经保护概念的有效性提供了鼓励。有多种新的神经保护化合物正处于研究的早期阶段，只要遵循适当的临床前开发指南，其中一些可能在临床上被证明是有效的。
