E.W. Harris* and R.J. Murray Pages 429 - 442 ( 14 )
A number of antagonists of the NMDA-selective ionotropic glutamate receptor have been synthesized and evaluated in animals and in man. Several compounds that bind to the "MK-801 site" within the NMDA-receptor channel have been tested in animals, and some in man. Although these compounds have a common pharmacological action, there are surprising differences in the safety profiles within this single class of NMDA-antagonists. The reasons for this heterogeneity are unclear, but may result from preferential selectivity for different NMDA-receptor subtypes, of which there are many, differences in the kinetics of NMDA-receptor block, or possibly the existence of multiple modes of channel block. These issues, possible underlying structural correlates, and prospects for being able to optimize NMDA channel blockers with regard to their safety profile are discussed.