EXCITATORY AMINO-ACID ANTAGONISTS, LAMOTRIGINE AND BW-1003C87 AS ANTICONVULSANTS IN THE GENETICALLY EPILEPSY-PRONE RAT

Sound-induced seizures in genetically epilepsy-prone rats were used to compare the anticonvulsant effect of phenytoin and diazepam with comp ounds which decrease glutamatergic neurotransmission including excitat ory amino acid antagonists acting at N-methyl-D-aspartate (NMDA) recep tors: D(-)CPPene, CGP 37849 and MK 801 or at the glycine/NMDA site: AC PC (1-aminocyclopropane-dicarboxylic acid) (partial agonist) or non-NM DA receptors: NBQX -dihydroxy-6-nitro-7-sulfamoylbenzo[f]-quinoxaline . Li) and GYKI 52466 4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazepin e - HCI) or acting at sodium channels to decrease glutamate release: l amotrigine and BW 1003C87 (5(2,3,5-trichlorophenyl)-2,4-diaminopyrimid ine ethane sulphonate). ED50 values against clonic seizures (in mumol/ kg at the time of peak anticonvulsant effect) were: phenytoin 30.5 (2 h), diazepam 0.5 (0.5 h), MK 801 0.01 (4 h), D(-)CPPene 1.9 (4 h), CGP 37849 2 (1 h), GYKI 52466 24 (0.25 h), NBQX 40 (0.5 h), ACPC 1053 (0. 5 h), BW 1003C87 2.2 (1 h), lamotrigine 4.8 (4 h). BW 1003C87, lamotri gine, MK 801, phenytoin, diazepam and CGP 37849 had the most favourabl e therapeutic indices (rotarod locomotor deficit ED50/anticonvulsant E D50).