INFLUENCE OF CHRONIC AMINOPHYLLINE ON ANTIELECTROSHOCK ACTIVITY OF DIAZEPAM AND AMINOPHYLLINE-INDUCED CONVULSIONS IN MICE

The effects of chronic administration of aminophylline (AMPH; 50 mg/kg , twice daily for 14 consecutive days) were studied on both antielectr oshock efficacy of diazepam (DZP) and convulsive activity of AMPH in m ice. AMPH injected acutely at a dose of 50 mg/kg significantly reduced anticonvulsant action of DZP elevating ED(50) from 10.9 (control) to 15.9 mg/kg (p < 0.01). After the administration of AMPH for 3 days, ED (50) value was still higher compared with control. Chronic treatment w ith AMPH resulted in further increase of ED(50) of DZP, which was 20.2 mg/kg, and this elevation was significant not only when compared with saline-treated animals, but also with acute and 3-day administration of the xanthine (p < 0.01, 0.05, and 0.001, respectively). Therefore, no tolerance to this AMPH-mediated effect was found, and even an enhan cing influence was observed. On the other hand, chronic treatment with AMPH decreased convulsive activity of AMPH elevating ED(50) for induc tion of clonic seizures from 218 to 252 mg/kg (p < 0.01). The remainin g seizure parameters were unaffected. Furthermore, in both cases pharm acokinetic interactions were excluded, at least in terms of total plas ma levels of the drugs. The results suggest that the mechanisms govern ing AMPH-induced reversal of the anticonvulsant efficacy of DZP qualit atively differ from those underlying AMPH-induced convulsions. Moreove r, these data support the claim that AMPH should be avoided in patient s suffering from different types of epilepsy.