The Glycine Coagonist Site of the NMDA Receptor

The discovery of the glycine binding site on the NMDA receptor (Johnson and Ascher, 1987) is recognized as a highly significant event by those interested in receptor-channel mechanisms. It also offers a new target site in drug development for the treatment of neuropa-thologies associated with NMDA receptor activation. The list of neural dysfunctions mediated in part by. synaptic activation of NMDA receptors very likely includes epileptiform seizures (Croucher et al., 1982) and brain damage induced by ischemia or hypoxia in some models (Simon et al., 1984). Growing evidence indicates however that NMDA receptor activation is important also for establishing certain neuronal connections during development (Tsumoto et al., 1987; Kleinschmidt et al., 1987; Lincoln et al., 1988) and has been implicated in some types of learning or memory (Morris et al., 1986). Thus both agonists and antagonists of the NMDA receptor may find clinical utility in the future. Currently available NMDA receptor blockers, acting either at the glutamate binding site or the open ion channel, either have difficulty penetrating the blood-brain barrier or have unacceptable side effects such as psychosis. The glycine site appears to present a pharmacology sufficiently different from that of the other binding sites on the NMDA receptor to offer a novel target for new drug discovery.