Metabotropic glutamate receptor agonists reduce epileptiform activity in the rat cortex.
Slices of rat cingulate cortex, when incubated in magnesium-free medium, produce spontaneous epileptiform spikes. Here it is demonstrated that the metabotropic glutamate receptor (mGluR) agonists +/- trans-1-amino-cyclopentane-1,3-dicarboxylic acid (+/- Trans-ACPD), IS3R-ACPD and quisqualic acid (quis) can reduce the frequency of these bursts in a concentration-dependent manner. The IC50 values were 16, 12 and 26 microM, respectively. The low concentrations of +/- trans- and IS3R-ACPD used, plus the lack of NMDA antagonism shown by these compounds, suggest that the effect may be via a presynaptic reduction in glutamate release. The relative potency of the agonists IS3R-ACPD > Trans-ACPD > quis would seem to suggest that the mGluR1 receptor is not involved.
Sheardown
M J
MJ
Novo Nordisk A/S, CNS Discovery, Pharmaceutical Research, Måløv, Denmark.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004827:Epilepsy / Q000517:prevention & control*; D018691:Excitatory Amino Acid Antagonists; D066298:In Vitro Techniques; D008297:Male; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016318:Quisqualic Acid