PROFILE OF ANTICONVULSANT ACTIVITY AND MINIMAL TOXICITY OF METHYL OPHENYL)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 ophenyl)amino]-6-met hyl-2-oxo-cyclohex-3-en-1-oate (ADD 196022), were compared with those of phenytoin (PI-IT), carbamazepine (CBZ), and valproate (VPA). These compounds were evaluated in mice and rats using well-standardized anti convulsant testing procedures. Results indicate that ADD 196022 is a v ery potent anticonvulsant in the maximal electroshock seizure (MES) mo del. The compound was effective in nontoxic doses after intraperitonea l (i.p.) administration in mice and oral administration in rats. In mi ce, i.p. administration of ADD 196022 resulted in an ED(50) value of 2 6.2 mg/kg as compared with a value of 6.48 mg/kg for PHT in the same a ssay. ADD 196022 was more potent that PHT in the oral rat model, havin g an ED(50) 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 mo dels evaluated and thus has a pharmacologic profile similar to that of PHT.