Anticonvulsant properties of spirohydantoins derived from optical isomers of camphor

Natural camphor exists as the d (+) form but the l (-) form has been synthesized. Replacement of the keto group on carbon 2 of each form with a hydantoin moiety led to only one spirohydantoin derivative. Both d and l derivatives were synthesized. Both forms and their racemic mixture were tested in vivo for toxicity and behavioral effects in mice. A dose of 100 mg/kg of the d form was not toxic: mice showed normal grooming and exploratory behavior; the l form induced hunched posture, body jerks and myoclonic manifestations followed by quiescence. The dl form showed intermediate effects. Challenge with the convulsant pentylenetetrazol (Metrazol) 2 hr after treatment with placebo or the camphor spirohydantoins produced seizure manifestations in all controls, in half of the subjects pretreated with the d-camphor derivative, in none of those pretreated with the l derivative and an intermediate response in those pretreated with racemic mixture. Thus, a spirohydantoin moiety added to camphor conferred strong anticonvulsive properties on the l form and modest ones on the d form; the d form did not seem to antagonize the l form.