Antiepileptic effects of the excitatory amino acid antagonist cis-2,3 piperidine-dicarboxylic acid depend on non-N-methyl-d-aspartate receptors.
The effects of the broad spectrum antagonist of the excitatory amino acid neurotransmission, the cis-2,3 piperidine-dicarboxylic acid (cis-2,3 PDA) were investigated on the epileptiform activity induced in vitro by different treatments on rat hippocampal slices. The drug reduced the bursting duration by 45% and the occurrence of the additional population spikes by 50% compared with controls using 1 microM kainic acid to induce epileptiform bursting. At the same concentrations (50-100 microM) cis-2,3 PDA did not significantly affect the magnesium free-induced epileptiform activity. At higher concentrations (200-400 microM), the drug was able to reduce by 25% the bursting duration and the occurrence of the additional population spikes using 1 mM penicillin to induce epileptiform bursting. Our data indicate that the broad spectrum antagonist of the excitatory amino acid transmission, cis-2,3 PDA, presents a low antiepileptic activity that could be related to an influence on "non N-methyl-d-aspartate" (NMDA) receptors.
Sagratella
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Laboratoire di Farmacologia, Instituto Superiore di Sanità, Roma, Italy.
Frank
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de Carolis
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D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010406:Penicillins / Q000494:pharmacology; D010477:Perfusion; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D000927:Anticonvulsants; D010406:Penicillins; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C029262:2,3-piperidinedicarboxylic acid; D008274:Magnesium; D007608:Kainic Acid