Combined strategies for the discovery of ionotropic glutamate receptor antagonists.
New glutamate receptor ligands: This review describes the discovery of rationally designed AMPA and NMDA receptor antagonists, some of which have been proven to be highly potent anticonvulsant and neuroprotective agents.This review summarizes the results of our research group engaged in the development of new glutamate receptor ligands. Chemical and biological studies of several active molecules have been carried out. In particular, extensive work has addressed the identification of antagonists of AMPA and NMDA receptor subtypes using a combination of computational strategies. Innovative synthetic pathways have been used and small libraries of new molecules prepared. In vitro and in vivo tests were performed, and some compounds proved to be highly potent anticonvulsant and neuroprotective agents.
Chimirri
Alba
A
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. chimirri@pharma.unime.it
De Luca
Laura
L
Ferro
Stefania
S
De Sarro
Giovanbattista
G
Ciranna
Lucia
L
Gitto
Rosaria
R
D000927:Anticonvulsants / Q000737:chemistry; D055808:Drug Discovery; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry*; D016202:N-Methylaspartate / Q000737:chemistry; D018696:Neuroprotective Agents / Q000737:chemistry; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000737:chemistry
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid