title: Interactions of excitatory amino acid antagonists with conventional antiepileptic drugs.
abstract: Excitatory amino acid antagonists possess anticonvulsant properties in many experimental models of epilepsy and were shown to potentiate the protective activity of conventional antiepileptics against maximal electroshock-induced seizures in mice. Combined treatments of valproate with either D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid or dizocilpine (NMDA antagonists), which provided a 50% protection against maximal electroshock, produced no side-effects, as measured in the chimney test (motor coordination) or passive avoidance task (long-term memory). Valproate alone at its ED50 against maximal electroshock, induced severe adverse effects. The NMDA antagonists, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid, memantine, procyclidine, and trihexyphenidyl also potentiated the protective activity of conventional antiepileptics but these treatments were associated with considerable side-effects. The non-NMDA receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline and 1-(amino-phenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine, also enhanced the anticonvulsive action of antiepileptic drugs against maximal electroshock, and these combinations generally resulted in no adverse effects. The potential clinical importance of some combinations of common antiepileptics with excitatory amino acid antagonists is postulated.
authors.affiliation: Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland.
authors.forename: S J
authors.initials: SJ
authors.lastname: Czuczwar
authors.forename: W A
authors.initials: WA
authors.lastname: Turski
authors.forename: Z
authors.initials: Z
authors.lastname: Kleinrok
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists