A Novel Class of Neuroprotective Agents for Stroke

描述(由申请者提供)：ADD234037以前的研究 (R-2-Acetamido-N-Benzyl-3-Methoxypropionamide)是一种官能化氨基酸衍生物，已证明具有抗惊厥和神经保护作用。该化合物目前正在进行第二阶段临床研究，以评估其在治疗癫痫和神经病理性疼痛方面的有效性。初步研究表明，ADD234037的类似物具有类似的抗惊厥活性。评估这些化合物的研究将在一年内取得进展 循序渐进的时尚。将进行进一步的研究，以确定每种化合物的受体亲和力。根据这些结果，选定的候选药物将在体外和活体模型中进行神经保护活性评估。将对该系列中最有趣的化合物进行安全评估。这一最后阶段的先导化合物将在中风的活体动物模型中进行测试。在讨论过程中提出了几点关切。例如，Harkoseride观察到的神经元损伤保护(在癫痫持续状态下穿孔路径刺激条件下)与缺血时的神经保护有何关系？此外，三支血管闭塞的缺血模型将产生更好、更具重复性的病变，这将是一种更可靠的缺血筛查模型。建议的模型提供了更多的病变可变性，这将使其在统计上更难检测到所选化合物的显著改善。三支血管闭塞的缺血模型将提供更好的、更具重复性的病变，这将是一种更可靠的缺血筛选模型。此外，Harkoseride(在癫痫持续状态患者中通过穿孔路径刺激)如何保护神经元损伤与缺血时的神经保护有关。

DESCRIPTION (provided by applicant): Previous studies with ADD234037 (R-2-Acetamido-N-Benzyl-3-Methoxypropionamide) a functionalized amino acid derivative, have demonstrated its anticonvulsant and neuroprotective properties. This compound is currently being evaluated in Phase II clinical studies for its utility in the treatment of epilepsy and neuropathic pain. Preliminary studies have demonstrated similar anticonvulsant activities with close analogs of ADD234037. Research to evaluate each of these compounds will progress in a stepwise fashion. Further studies will be undertaken to determine receptor affinities for each compound. Based upon these results, selected candidates will be evaluated for neuroprotective activity in in vitro and in viva models. Safety evaluation will be conducted on the most interesting compound in the series. The lead compound at this final stage will be tested in an in viva animal model of stroke. Several concerns were raised during the discussion. For example, how does the neuronal damage protection observed with harkoseride (under conditions of perforate path stimulation in status epilepticus) relate to neuroprotection in ischemia? Also, a three-vessel occlusion model of ischemia would yield better, more reproducible lesions, which would be a more reliable model for ischemia screening. The proposed model gives much more lesion variability, which would make it much more statistically difficult to detect a significant improvement with the selected compounds. A three-vessel occlusion model of ischemic would give better, more reproducible lesions, which would be a more reliable model for ischemia screening. Also, how does the neuronal damage protect with harkoseride (via perforate path stimulation in status epileptics) related to neuroprotection in ischemia.