Aminophylline and CGS 8216 Reverse the Protective Action of Diazepam Against Electroconvulsions in Mice

CGS 15943 A (a nonxanthine adenosine antagonist) was studied on the protective efficacy of carbamazepine (60 min prior to the convulsive test), diazepam (60 min), diphenylhydantoin (120 min), phenobarbital (120 min), and valproate (30 min) against maximal electroshock-induced convulsions in mice. Moreover, the influence of the adenosine antagonist on 2-chloroadenosine (1 mg/kg, 20 min prior to the test)- and valproate (250 mg/kg, 30 min)-induced inhibitions of locomotor activity was also studied. CGS 15943 A (1 mg/kg) was given 15 min before both tests and all the drugs were administered i.p.. The adenosine antagonist (1 mg/kg) remained without influence upon the protective activity of all studied antiepileptics, reflected by their respective ED50 values against maximal electroshock. However, both 2-chloroadenosine and valproate-induced inhibitions of locomotor activity were attenuated by CGS 15943 A, which alone did not affect this parameter. However, CGS 15943 A (5 mg/kg) diminished the protection offered by diphenylhydantoin, increasing its ED50 value from 13 to 16 mg/kg. It may be concluded that the protection provided by common antiepileptic drugs against electroconvulsions seems independent of adenosine-mediated inhibition. In the case of diphenylhydantoin, one may suggest the involvement of purinergic transmission in the final anticonvulsant effect.

Section: Discussionmentioning

confidence: 97%

Influence of CGS 15943 A (a nonxanthine adenosine antagonist) on the protection offered by a variety of antiepileptic drugs against maximal electroshock-induced seizures in mice

Czuczwar

Janusz

Szczepanik

et al. 1991

“…Aminophylline (up to 100 mg/kg; 0.476 mmol of anhydrous theophylline/kg) remained also without effect on the threshold, the result being obtained elsewhere (Czuczwar et al, 1985).…”

Section: Effect Of 8-(p-sulfophenyl) Theophylline On the Threshold Fomentioning

confidence: 87%

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

Borowicz

Kozicka

Kleinrok

et al. 1993

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.

“…There is well documented evidence that strychnine and aminophylline impaired the anticonvulsant potency of conventional antiepileptic drugs against maximal electroshock-induced seizures in mice (Czuczwar et al, 1985(Czuczwar et al, , 1986(Czuczwar et al, , 1987a(Czuczwar et al, , b, 1991. Further, any pharmacokinetic interactions, which could account for these effects, were not probable (Czuczwar et al, 1989(Czuczwar et al, , 1991.…”

Section: Discussionmentioning

confidence: 97%

“…However, it is not clear to what extent these mechanisms participate in the induction of seizure activity and whether there are any further mechanisms responsible for this phenomenon. Aminophylline was also reported to reverse the anticonvulsant action of various antiepileptic drugs against seizures induced by maximal electroshock or that of phenobarbital against amygdala-kindled seizures in rats (Czuczwar et al, 1985(Czuczwar et al, , 1986(Czuczwar et al, , 1987a(Czuczwar et al, ,b, 1989. (Aebischer et al, 1989) and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a non-competitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate (AMPA/KA) antagonist (Tarnawa et al, 1990;Donevan and Rogawski, 1993), have been recently tested in various models of experimental epilepsy (Smith et al, 1991;Rogawski, 1992;Tutka et al, 1992;Yamaguchi et al, 1993;Czuczwar et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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

Tutka

Turski

Kleinrok

et al. 1996

Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene-a competitive NMDA antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizures. The respective ED50 values of aminophylline were 55.7 and 98.4 mg/kg i.p. However, aminophylline (up to 100 mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4-methyl-7,8-methyl- enedioxy-5H-2,3-benzodiazepine (GYKI 52466-a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate against maximal electroshock-the ED50 values of strychnine for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproate were 0.082, 0.35 and 0.28 mg/kg s.c., respectively. An involvement of strychnine sensitive glycinergic receptor-mediated events in the mechanism of the anticonvulsive activity of excitatory amino acid antagonists and valproate may be postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering an advantage over conventional antiepileptics in patients with epilepsy, requiring aminophylline for pulmonary reasons.