Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, via Savinio, I-87036 Rende, CS, Italy.
Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, via Savinio, I-87036 Rende, CS, Italy.
Curr Opin Pharmacol. 2017 Aug;35:111-119. doi: 10.1016/j.coph.2017.07.014. Epub 2017 Aug 17.
The search for neuroprotection in acute ischemic stroke has been dramatically disappointing, with virtually all clinical trials failed for excessive toxicity or lack of efficacy of the tested drug; whereby, current treatments are exclusively based on reperfusion. Given the crucial role of amino acid neurotransmission in ischemic pathobiology, numerous failed strategies were aimed at blocking ionotropic glutamate receptor-mediated excitotoxicity or potentiating GABA-mediated inhibition. Recent work has revived the interest of pharmacologists toward glutamate and GABA receptors, due to a better understanding of subtype-specific toxicity and their involvement in ischemic tolerance. Thus, blocking receptor stimulation through glutamate grabbing, inhibiting downstream transduction pathways or selectively antagonizing detrimental NMDA receptor subpopulations represent promising strategies to rescue ischemic brain injury with limited side effects.
急性缺血性脑卒中的神经保护研究令人大失所望，几乎所有临床试验都因受试药物毒性过大或疗效不佳而失败；因此，目前的治疗方法完全基于再灌注。鉴于氨基酸神经递质传递在缺血性病理生理学中的关键作用，许多失败的策略旨在阻断离子型谷氨酸受体介导的兴奋性毒性或增强 GABA 介导的抑制作用。由于对亚型特异性毒性及其在缺血性耐受中的作用有了更深入的了解，谷氨酸和 GABA 受体再次引起了药理学家的兴趣。因此，通过谷氨酸抢夺阻断受体刺激、抑制下游转导途径或选择性拮抗有害的 NMDA 受体亚群，代表了一种具有有限副作用的抢救缺血性脑损伤的有前途的策略。
