Glycine Antagonists for Treatment of Ischemic Brain Injury

摘要: Pharmacologic antagonists of glutamate’s N-methyl-D-aspartate (NMDA) receptor complex have neuroprotective properties, however, the psychomimetic and sedative properties these agents limited their clinical development (1–4). Recent work has shown that activation NMDA involves glycine. Whereas glycine is an inhibitory neurotransmitter modulates activity in spinal cord inter-neurons, recent evidence there are additional binding sites can facilitate excitatory neurotransmission central nervous system (CNS). There experimental enhances NMDA-mediated responses neurons by acting at a distinct site within complex. A number compounds known to antagonize this site, thereby inhibiting responses. These offer great potential treatment stroke other causes CNS injury. Preclinical suggests also may not cause phencyclidine (PCP)-like side-effects seen with typical competitive noncompetitive antagonists. Although currently experience antagonists, preliminary data suggest well tolerated humans.