Acetylpheneturide

The anticonvulsant activity of Et α-phenylbutyrylallophanate (P-5257) and of its derivatives was studied in exptl. animals.P-5257 showed the lowest toxicity in mice and rats among the antiepileptics tested.P-5257 modified the spontaneous behavior of the animals at high doses.Its neurotoxicity was the lowest among phenurone derivatives P-5257 suppressed both elec. and Metrazol shocks in mice and rats, and these effects resembled those of phenurone, pheneturide, crampol, and phenobarbital.Neither development of tolerance nor a withdrawal effect in mice was observed during the daily administration of P-5257 for 3 weeks.The fact that the compound did not potentiate the hypnotic activity of barbiturate in mice was unique and differed from phenurone derivatives and other antiepileptics tested.In unanesthetized cats, the compound produced no effect on the spontaneous electroencephalogram, reticular arousal threshold, and pallidal seizure thresholds.No apparent blocking effect by the compound on either the cholinergic or adrenergic systems 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 leukopenia, proteinuria, mild nephrosis, and slight pyknotic fatty liver with heteromorphous cytoplasm.The relation between anticonvulsant activity and chem. structure of allophanate derivatives is discussed.