ANTICONVULSANT ACTIVITY OF CARBAMAZEPINE AND DIPHENYLHYDANTOIN AGAINST MAXIMAL ELECTROSHOCK IN MICE CHRONICALLY TREATED WITH AMINOPHYLLINE

The anticonvulsant activities of both carbamazepine and diphenylhydantoin alone (after a single intraperitoneal administration) or combined with aminophylline were studied against maximal electroshock-induced convulsions in male mice. Aminophylline (injected acutely at 50 mg/kg) significantly increased the ED50 values of both antiepileptics. Given for three days, aminophylline (50 mg/kg, twice daily) still impaired the potency of both antiepileptics and after chronic aminophylline administration a further decrease in the protective activity of carbamazepine and diphenylhydantoin was found. Specifically, after 14 days of aminophylline treatment, ED50s for carbamazepine and diphenylhydantoin were 26 and 19 mg/kg, respectively. These ED50s were significantly elevated compared to values determined after acute aminophylline treatment (21.2 and 14.9 mg/kg, respectively). Plasma levels of both antiepileptics were unaffected by chronic aminophylline which seems to exclude a pharmacokinetic interaction in terms of total plasma levels at least. The present results clearly indicate that the aminophylline-induced impairment of the anticonvulsant activity of carbamazepine and diphenylhydantoin is enhanced over time. This may render aminophylline a hazardous drug to epileptic patients who are prescribed this smooth muscle relaxant.