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.
Krogsgaard-Larsen
P
P
Department of Organic Chemistry, Royal Danish School of Pharmacy, Copenhagen.
Hansen
J J
JJ
D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D015195:Drug Design; D006801:Humans; D007051:Ibotenic Acid / Q000494:pharmacology*; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000187:drug effects*; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D007051:Ibotenic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate