Comparative anticonvulsant activity and neurotoxicity of 4-amino-N-(2,6-dimethylphenyl)benzamide and prototype antiepileptic drugs in mice and rats.
The anticonvulsant and toxic properties of 4-amino-N-(2,6-dimethylphenyl)benzamide, (ADD 75073), were compared with phenytoin (PHT), phenobarbital (PB), ethosuximide (ESM), and valproate (VPA). These compounds were evaluated in mice and rats using well-standardized anticonvulsant test procedures. The results indicate that ADD 75073 is a very potent anticonvulsant in the maximal electroshock seizure (MES) model. The compound was effective in nontoxic doses following intraperitoneal (i.p.) administration in mice and oral administration in both mice and rats. In mice, the i.p. administration of ADD 75073 resulted in an ED50 value of 2.6 mg/kg as compared with a value of 9.5 mg/kg for phenytoin (PHT) in the same assay. Compound ADD 75073 was ineffective in nontoxic doses against all other seizure models examined in this study, and thus has a pharmacologic profile similar to that of PHT.
Clark
C R
CR
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Alabama 36849.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology* / Q000633:toxicity; D004597:Electroshock; D005013:Ethosuximide / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010852:Picrotoxin; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013331:Strychnine; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D001549:Benzamides; D005013:Ethosuximide; D010634:Phenobarbital; D010672:Phenytoin; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013331:Strychnine; D014635:Valproic Acid; C055323:ameltolide