Naturally-occurring excitatory amino acids as neurotoxins and leads in drug design.

The central excitatory neurotransmitter (S)-glutamic acid (Glu) activates at least three types of receptors the NMDA, AMPA, and kainic acid (KAIN) receptors. These receptors mediate the neurotoxicity of a number of naturally-occurring Glu analogues. Thus, domoic acid, a KAIN receptor agonist, has probably been the cause of severe neurologic illness in people who consumed domoic acid poisoned food. beta-N-oxalylaminoalanine (beta-ODAP), an AMPA receptor agonist, has been associated with lathyrism, a spastic paraparesis caused by dietary intake of Lathyrus sativus. The neurotoxic Amanita muscaria constituent ibotenic acid, a nonselective NMDA receptor agonist, has been used as a lead structure for the development of the specific NMDA receptor agonist AMAA, AMPA, and a number of therapeutically interesting AMPA and KAIN receptor agonists.