THE ANTICONVULSANT ACTIVITY OF ETHYL α-PHENYLBUTYROYL ALLOPHANATE (P-5257)

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Abstract
The anticonvulsant activity of ethyl [alpha]-phenylbutyroyl allophanate (P-5257) and its derivatives were studied in experimental animals. P-5257 showed one of the least acute lethal toxicity in mice and rats among the anti-epileptics tested. P-5257 modified slightly the spontaneous behavior of the animals at high doses. Its neurotoxicity was the least among phenu-rone derivatives. P-5257 suppressed significantly both electro- and metrazol-shocks in mice and rats, and these effects resembled to those of phenurone, pheneturide, crampol and phenobarbital. Neither development of tolerance nor withdrawal effect in mice was observed during the daily administration of P-5257 for 3 weeks. The result that the compound did not potentiate the hypnotic activity of barbiturate in mice, indicated the unique effect which differed from phenurone derivatives and other antiepileptics tested. Electroencephalographic (EEG) studies in unanesthetized cats showed that the compound produced no effect on the spontaneous EEG, reticular arousal threshold, and hippocampal and pallidal seizure thresholds. No apparent blocking effect of the compound on either cholinergic or adrenergic system was observed in unanesthetized spinal or nembutalized cats. Subchronic toxicological studies on P-5257 indicated no significant effect upon growth rate, blood and urine analysis, and the tissues of rats and mice. While, phenurone caused a slight decrease in growth rate, mild leucopenia, proteinuria, mild nephrosis and slight picnotic fatty liver with heteromorphous cytoplasma. The relationship between anticonvulsant activity and chemical structure of allophanate derivatives was discussed.