The effect of trans-resveratrol (resveratrol), a polyphenolic compound with potent antioxidant activity, was investigated against pentylenetetrazole (PTZ) induced seizures in rats. Resveratrol (20, 40, and 80 mg/kg i.p.) administered 20 min prior to convulsive challenge with PTZ (60 mg/kg i.p.) dose dependently reduced the percent incidence of generalized tonic-clonic convulsions. Resveratrol (40 mg/kg) also potentiated the effect of sodium valproate (150 mg/kg) and diazepam (2 mg/kg) against PTZ-induced seizures. Since adenosine, an endogenous anticonvulsant, has been demonstrated to modulate the action of various antiepileptics, experiments were also carried out to determine whether an adenosinergic mechanism is involved in the anticonvulsant action of resveratrol. When a subanticonvulsant dose of adenosine (500 mg/kg) was administered together with resveratrol, a significant reduction in the percent incidence of generalized tonic-clonic convulsions was observed. Moreover, the nonspecific adenosine receptor antagonist theophylline (50 mg/kg i.p.) significantly reversed the resveratrol-induced protection, whereas the specific adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (1 mg/kg i.p.) could not reverse the resveratrol-induced protection. The findings of the present study suggest an antiepileptic potential of resveratrol and that an adenosinergic mechanism may play a role in its anticonvulsant activity.

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