Influence of aminophylline and 8-(p-sulfophenyl)theophylline on the anticonvulsive action of diphenylhydantoin, phenobarbital, and valproate against maximal electroshock-induced convulsions in mice

Abstract

Aminophylline (theophylline2.ethylenediamine) in the dose of 12.5 mg/kg (i.p.) was ineffective upon all antiepileptic drugs studied and at the higher dose of 25 mg/kg, impaired the anticonvulsant action of phenobarbital and valproate against maximal electroshock in mice. The protection offered by diphenylhydantoin was diminished by aminophylline at 50 mg/kg (0.238 mmol of anhydrous theophylline/kg). In contrast, 8-(p-sulfophenyl)theophylline (a theophylline derivative unable to cross the blood-brain barrier) in the dose of 80 mg/kg (0.238 mmol/kg) did not influence the protective activity of diphenylhydantoin, phenobarbital, and valproate. It might be concluded that the aminophylline-induced impairment of the anticonvulsant action of common antiepileptic drugs results from the central effects of this methylxanthine.

Influence of aminophylline and strychnine on the protective activity of excitatory amino acid antagonists against maximal electroshock-induced convulsions in mice

“…An alternative way to manage the problem of obturative lung diseases in epileptic patients might be focused on a search for other than aminophylline xanthine derivatives that do not interfere with the protective efficacy of antiepileptic drugs. As a matter of fact, enprofylline (3-propylxanthine) and 8-(p-sulfophenyl)-theophylline seem to fulfil this criterion (Borowicz et al, 1993;Czuczwar et al, 1987a, b).…”

Influence of a potential anti-asthmatic drug, CR 2039, upon the anticonvulsive activity of conventional antiepileptics against maximal electroshock-induced seizures in mice

“…The experimental data, on the other hand, have provided evidence that aminophylline at therapeutic doses may interfere with the anticonvulsive activity of conventional antiepileptics against electroconvulsions. Specifically, aminophylline distinctly impaired the protective efficacy of carbamazepine, diazepam, diphenylhydantoin, phenobarbital, and valproate (Borowicz et al, 1993;Czuczwar et al, 1985Czuczwar et al, , 1986Czuczwar et al, , 1989. Interestingly, no tolerance developed towards this particular activity of aminophylline and its hazardous influence upon antiepileptic drugs was enhanced over time (Wla2 et al, 1992(Wla2 et al, , 1993(Wla2 et al, , 1994.…”

“…Furthermore, potential anti-asthmatic drugs may be related to xanthine derivatives which do not enter the central nervous system. Specifically, 8-(p-sulfophenyl)theophylline, similarly to enprofylline, did not impair the protection offered by conventional antiepileptics against maximal electroshock-induced seizures (Borowicz et al, 1993). Another approach would assume a search for a safe anti-asthmatic among agents unrelated to xanthine derivatives.…”