ANTICONVULSANT AND TOXICOLOGIC PROPERTIES OF SOME BENZILIC AMIDES AND THE PHYSIOLOGICAL DISPOSITION OF THE N-ETHYL DERIVATIVE

¹ Research Laboratories, Mead Johnson & Company, Evansville, Indiana
² Department of Pharmacology, Warner-Lambert Research Institute, Morris Plains, New Jersey

The aniticonvulsant properties and toxicities of benzilic amide and a series of its N-substituted derivatives were studied. The parent compound and its methyl, ethyl and isopropyl analogues had marked activity in protecting against maximal electroshock seizures. These agents, with the exception of N-methyl benzilic amide, also demonstrated similar activity against pentylenetetrazol (Metrazol) convulsions. Unsubstituted benzilic amide was the most potent against both types of seizures, while the N-ethyl and N-isopropyl derivatives, due to their lower neurotoxicities, had optimal protective indices w-hen measured against both convulsions.

With the aid of an anualytical method developed for the estimation of N-ethyl benzilic amide, its physiological disposition was investigated in rats and mice. Approximately one-third of an oral dose could be accounted for in the urine, but the nature of the urinary excretory products was incompletely known. One of these products of metabolism was demonstrated to be benzilic amide. The role of benzilic amide in the pharmacodynamic activity of N-ethyl benzilic amide and the importance of N-dealkylation in the production of tolerance to the action of the amide were discussed.