Non-competitive antagonists of excitatory amino acid receptors

The ability of the non-competitive NMDA receptor antagonists to penetrate the brain following systemic administration, and the use-dependency of their antagonism may confer distinct therapeutic advantages in the treatment of neurological disorders where an overstimulation of NMDA receptors is thought to occur.

Abstract

Non-competitive antagonists have become important tools for investigating the basic mechanisms of NMDA receptor function. Such compounds (e.g. MK-801, PCP) are thought to act at the level of the NMDA receptor-associated ion channel and many show a marked use-dependence in their antagonist properties. Little information is available concerning selective non-competitive antagonists of quisqualate or kainate receptors. A number of structurally diverse compounds act as non-competitive antagonists of glutamate receptors at invertebrate neuromuscular junctions, although it remains to be determined whether these compounds have effects at excitatory amino acid receptors in the mammalian CNS. The ability of the non-competitive NMDA receptor antagonists to penetrate the brain following systemic administration, and the use-dependency of their antagonism may confer distinct therapeutic advantages in the treatment of neurological disorders where an overstimulation of NMDA receptors is thought to occur (such as in epilepsy or cerebral ischaemia).