Profile of anticonvulsant activity and minimal toxicity of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate and some prototype antiepileptic drugs in mice and rats.
The anticonvulsant and toxic properties of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate (ADD 196022), were compared with those of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). These compounds were evaluated in mice and rats using well-standardized anticonvulsant testing procedures. Results indicate that ADD 196022 is a very potent anticonvulsant in the maximal electroshock seizure (MES) model. The compound was effective in nontoxic doses after intraperitoneal (i.p.) administration in mice and oral administration in rats. In mice, i.p. administration of ADD 196022 resulted in an ED50 value of 26.2 mg/kg as compared with a value of 6.48 mg/kg for PHT in the same assay. ADD 196022 was more potent that PHT in the oral rat model, having an ED50 value of 5.79 mg/kg as compared to 23.2 mg/kg for PHT. ADD 196022 was ineffective in nontoxic doses against all other seizure models evaluated and thus has a pharmacologic profile similar to that of PHT.
Mulzac
D
D
Department of Medicinal Chemistry, College of Pharmacy and Pharmacal Sciences, Howard University, Washington, D.C. 20059.
Scott
K R
KR
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002220:Carbamazepine / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D003514:Cyclohexylamines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004597:Electroshock; D004827:Epilepsy / Q000139:chemically induced / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D003514:Cyclohexylamines; C082302:ADD 196022; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010433:Pentylenetetrazole