Subtype selectivity

A great deal of work has been put into developing neuroprotectants targeting glutamate-gated ion channels, which include NMDA, AMPA and kainate, based on their central role in synaptic transmission in the CNS. Much of this work has focused on NMDA receptor antagonists. However, results have been disappointing due to adverse CNS effects (see BioCentury, June 16, 2003).

Last week, TorreyPines Therapeutics Inc. reported that its small molecule antagonist targeting specific subtypes of the AMPA and kainate glutamate receptors was found to be safe in a Phase I trial, adding to a safety profile established in earlier trials by Eli Lilly and Co. Moreover, according to President and CEO Neil Kurtz, "because we know that these three receptors only exist in the CNS, that means it will have no functional activity anywhere else and should be devoid of any peripheral activity." ...