The effects of
adenosine receptor agonists and antagonists were studied in
pentylenetetrazole (PTZ)-induced
seizures in rats. Animals were pretreated with the non-specific
adenosine receptor antagonist,
theophylline (50 and 100 mg/kg, i.p.), or the specific A(1)
adenosine receptor antagonist,
8-cyclopentyl-1,3-dipropylxanthine (
DPCPX), in a dose of 1 mg/kg, i.p., followed by 100%
anticonvulsant doses of
diazepam (4 mg/kg)/
sodium valproate (300 mg/kg, i.p.). Subsequently, they were challenged with
convulsant doses of PTZ i.e. 60 mg/kg, i.p. It was seen that while
DPCPX could not reverse the protection of both the
antiepileptic drugs,
theophylline significantly reversed this protection, as assessed by percent incidence of
seizures and change in latency parameters. In another set of experiments, the rats were pretreated with a combination of subanticonvulsant doses of
adenosine (500 mg/kg) or specific
adenosine A(1) receptor agonist, cyclopentyladenosine (CPA) and
diazepam (0.5 and 1 mg/kg)/
sodium valproate (150 mg/kg), prior to PTZ challenge. We observed a decrease in incidence and increase in latency of
seizures following either combination. The protection observed was independent of the hypothermic and hypotensive effects of
adenosine and CPA. These results indicate that though A(1) agonist enhances the protection of
diazepam and
sodium valproate, a direct involvement of
adenosine A(1) receptor in
anticonvulsant action of these drugs is doubtful.