Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.
三取代和四取代的
胍基化合物具有高结合亲和力,可与苯环
哌啶(PCP)受体结合,并更倾向于低亲和力与大脑西格玛受体结合。这些
胍基衍
生物作为非竞争性
抑制剂,通过阻断N
MDA受体离子通道复合物的离子通道作用,从而抑制谷
氨酸诱导的N
MDA受体反应。这些化合物因此具有神经保护作用,并可用于治疗缺氧、低血糖、脑或脊髓缺血、脑或脊髓创伤以及癫痫、阿尔茨海默病、肌萎缩性侧索硬化、帕
金森病、亨廷顿病、唐氏综合症、科萨科夫病和其他神经退行性疾病的治疗。