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.
D000818:Animals; D000927:Anticonvulsants; D002164:Camphor / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004311:Double-Blind Method; D006827:Hydantoins / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013237:Stereoisomerism
D000927:Anticonvulsants; D006827:Hydantoins; C051601:camphor-2-spirohydantoin; D002164:Camphor; D010433:Pentylenetetrazole