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

概要

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Cyclic derivatives of barbiturates (1, 2), hydantoins (3, 4), oxazolidines (5, 6), succinimides (7) and straight-chain derivatives of phenylacetylurea (8-10) have widely been used as the therapeutic antiepileptics. Phenylacetylurea (phenurone) was introduced by opening the hydantoin ring. The compound has been shown being a unique anticonvulsant for the treatment of the psychomotor epilepsy which had been relatively refractory to the other antiepileptics (11, 12). However, a number of side effects such as gastrointestinal disturbance, hepatotoxicity and personality disturbance, all inherent to the compound have limited the clinical use (11, 13). Further studies for the elimination of the side effects of the phenurone have introduced pheneturide (9) and N-acetyl pheneturide (crampol) (10) which still showed some similar side effects.<BR> Looking for less toxic and more effective anticonvulsant extensive studies of a series of allophanate compounds have chemically and pharmacologically been in succession in this laboratory. Among the derivatives studied, ethyl α-phenylbutyroyl allophanate (P-5257) has proved considerably unique in the anticonvulsant activity being highly potent, longer-durating and less toxic. The pharmacological effects of the compound compared with those of the derivatives of phenurone are described in the present report.