Expert opinion on investigational drugs
-
The N-methyl-D-aspartate (NMDA) receptor is a ligand-gated ion channel which is widely distributed in the central nervous system (CNS), and which mediates most of the fast excitatory neuronal transmission in the CNS. As with other ligand-gated ion channels, the NMDA receptor is a macromolecular complex which possesses a number of intricate regulatory sites within and around a central ion channel. The key regulatory components for which prototypic antagonists have been developed are the competitive NMDA antagonist binding site, the non-competitive NMDA antagonist binding site within the ion channel, and the NMDA receptor-associated glycine antagonist site. ⋯ It has not been disclosed if CP-101,606 possesses this dose-limiting side-effect. In summary, strategies for drug design and development based on our knowledge of the NMDA receptor complex have led to the development of a new generation of compounds for the treatment of stroke and traumatic brain injury, which remain to be evaluated in the clinic. The success of this approach will be defined in the next two to three years.