CHRONIC CAFFEINE AND THE ANTICONVULSANT POTENCY OF ANTIEPILEPTIC DRUGS AGAINST MAXIMAL ELECTROSHOCK

The anticonvulsant activities of intraperitoneally (IF) given carbamaz epine (CBZ) or diphenylhydantoin (DPH), expressed as their respective ED(50) values in mg/kg, were assessed after caffeine (CAFF) treatment against maximal electroshock-induced seizures in mice. CAFF was admini stered IP either in a single dose or every 12 h for 3 (subchronic CAFF ) and 14 days (chronic CAFF). Moreover, the protective activity of the antiepileptics was determined in mice which, following chronic CAFF, received a challenge dose of CAFF after either 24 or 72 h since CAFF w ithdrawal. A significant reduction of the protective efficacy of CBZ w as observed after chronic CAFF treatment (in a dose of 11.55 mg/kg), w hile a single dose and a 3-day treatment did not alter the action of C BZ. In case of CAFF (23.1 mg/kg), a significant elevation of CBZ's ED( 50) value was noted after 3- and 14-day treatments with CAFF. In contr ast, chronic CAFF (23.1-46.2 mg/kg) decreased the anticonvulsive activ ity of DPH to the same extent as did acute CAFF. Moreover, the ED(50) values for both, CBZ and DPH, evaluated 24 h after a 14-day treatment with CAFF (in doses of 23.1 and 46.2 mg/kg, respectively), were signif icantly elevated compared to respective control groups. A strong impai rment of the anticon-vulsant action of CBZ and DPH was observed when a challenge dose of CAFF was injected following either 24 or 72 h injec tion-free time. Pharmacokinetic interactions do not seem to explain th e obtained results in terms of total plasma levels of the antiepilepti cs after chronic treatment with CAFF. Our results may suggest that epi leptic patients should avoid CAFF-containing beverages and medicines.