Evaluation of anticonvulsants in barbiturate withdrawal

Four prototypic anticonvulsants were tested for their effectiveness against barbiturate withdrawal in cats. The effects were evaluated on a total of over 20 motor, autonomic and behavioral withdrawal signs. The animals were made physically dependent by 5 weeks of twice daily "maximally tolerable" sodium pentobarbital dosing intragastrically. Anticonvulsants were administered by intravenous infusion 25 hours after the final dose of chronic pentobarbital treatment when all withdrawal signs had become severe and grand mal type withdrawal convulsions were observed. Phenobarbital blocked withdrawal signs quite effectively at doses that caused no significant acute central nervous system depression. Trimethadione also reversed most withdrawal signs, but some signs persisted even at doses causing overt acute toxicity. Dimethadione was less effective than the parent compound, trimethadione, in reversing withdrawal but caused greater acute toxicity. Phenytoin was in effective for most withdrawal signs and some signs were made worse. The clonic phase of withdrawal convulsions was accentuated and the overall condition of the animals worsened. During withdrawal, the animals were less sensitive (tolerant) to phenobarbital but were more sensitive to acute toxicity from the other drugs tested.