New perspectives for the development of selective metabotropic glutamate receptor ligands.
The metabotropic glutamate receptors are GTP-binding-protein (G-protein) coupled receptors that play important roles in regulating the activity of many synapses in the central nervous system. As such, these receptors are involved in a wide number of physiological and pathological processes. Within the last few years, new potent and selective agonists and antagonists as well as radioligands acting on these receptors have been developed. Molecular modeling studies revealed the structural features of the glutamate binding site, and will be useful for the design of more selective and potent ligands. More interestingly, recent data revealed new regulatory sites on the receptor protein, able either to decrease or potentiate the action of the endogenous ligand. No doubt that in the near future a multitude of new tools to modulate the activity of these receptors will be discovered, enabling the identification of the possible therapeutic applications for these new neuroactive molecules.
Pin
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JP
Centre INSERM-CNRS de Pharmacologie-Endocrinologie, UPR 9023-CNRS, Laboratoire des Mécanismes Moléculaires des Communications Cellulaires, Montpellier, France. pin@ccipe.montp.inserm.fr
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D000818:Animals; D001665:Binding Sites; D005544:Forecasting; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009422:Nervous System Diseases / Q000188:drug therapy; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
D008024:Ligands; D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; D019204:GTP-Binding Proteins