Benzyleugenol (BE), a phenylpropene derivative, protects rats and mice against maximal electroshock seizures and has a protective index superior to that of phenobarbital. The present paper describes experiments carried out to further characterize the pharmacological and toxicological profile of this compound. 2. BE, at a dose range of 100-400 mg/kg ip, was inactive when tested for the following effects: analgesia, as measured by the hot plate and acetic acid writhing methods; neuroleptic-like effects, when tested by the catalepsy and palpebral ptosis, conditioned avoidance response and apomorphine-induced stereotypies methods; and anxiolytic effects, measured by the shock-elicited aggressiveness of mice. In contrast, tolerance to the anticonvulsant effect of BE, at dose range of 240-800 mg/kg orally, developed in mice and rats after 10 to 40 days of continued treatment. 3. BE, at dose range of 104-800 mg/kg orally, proved to be remarkably safe when chronically administered to laboratory animals. Thus, 3 to 6 month administration of large BE doses to rats and mice did not affect body weight, behavioral measures, serum and blood tests, or hematological parameters. Anatomopathological examinations of viscera of BE-treated animals did not reveal alterations which could be attributed to drug treatment. 4. Daily treatment up to 3 months of male rats and mice with BE, at a dose range of 80-800 mg/kg orally, did not affect the reproductive capacity of the animals. Pregnant females treated with BE during different periods of gestation gave birth to litters similar to those of control females; when adult, BE and control litters performed equally well in a passive avoidance task. 5. These results were compared with those of known anti-epileptic drugs, such as phenytoin, phenobarbital and valproic acid, and it is suggested that BE deserves further research as a potential candidate for the treatment of epilepsy.
