Perspectives for the use of excitatory amino acid ionotropic receptor antagonists as antiepileptic drugs.
Numerous antagonists of glutamate, belonging to N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists, were demonstrated to display anticonvulsant activity in various models of experimental epilepsy. Also, the glutamate antagonists enhanced the protective activity of conventional antiepileptic drugs against maximal electroshock-induced seizures in mice. However, some combinations of conventional antiepileptics with NMDA receptor antagonists resulted in profound adverse effects. In contrast, the antagonists for the non-NMDA receptor group potentiated the anticonvulsant activity of conventional antiepileptics, with no side-effects being observed. In some cases, the combined treatments were superior to the administration of an antiepileptic drugs alone, as regards adverse effects. In no case, glutamate antagonists affected the plasma levels of antiepileptic drugs. These data seem to indicate that non-NMDA receptor antagonists bear more important clinical potential as adjuvant antiepileptic drugs.
Czuczwar
S J
SJ
Department of Pharmacology and Toxicology, Medical University, Lublin, Poland. czuczwar@galen.imw.lublin.pl
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D018698:Glutamic Acid