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Eur J Pharmacol. 1997 May 30;327(2-3):109-15.

Prolonged anticonvulsant action of glutamate metabotropic receptor agonists in inferior colliculus of genetically epilepsy-prone rats.

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Department of Clinical Neurosciences, Institute of Psychiatry, London, UK.


The anticonvulsant activity of (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) (an antagonist of Group I and an agonist of Group II metabotropic glutamate (mGlu) receptors), of (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD) (an agonist of Group II mGlu receptors), and of L-serine-O-phosphate (an agonist of Group III mGlu receptors) was studied against sound-induced seizures in genetically epilepsy-prone (GEP) rats following bilateral microinjection into the inferior colliculus. All 3 drugs produce dose-dependent suppression of all phases of sound-induced seizures (wild running, clonic and tonic). (S)-4C3HPG produces an immediate and short-lasting (< 2 h) protection against sound-induced seizures with an ED50 value of 4.3 (3.2-5.7) nmol, at 5 min. The preferential agonists of Group II and Group III mGlu receptors produce an immediate, transient (< 10 min) proconvulsant effect followed by a prolonged (> 1 day) anticonvulsant effect against sound-induced seizures. The anticonvulsant ED50 value for (1S,3S)-ACPD is 9 (5-18) nmol at 2 h, and for L-serine-O-phosphate is 36 (6.5-199) nmol at 2 days. It is concluded that mGlu receptor activation potently modifies seizure threshold.

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