Seizure suppression by adenosine A2A receptor activation in a rat model of audiogenic brainstem epilepsy

Adenosine is known to suppress seizure activity mainly by activation of adenosine A1 receptors. However, little is known about the potential involvement of other types of adenosine receptors in seizure suppression. It was now tested whether activation of adenosine A2A receptors would be effective in the suppression of generalized brainstem seizures. Genetically epilepsy-prone rats were intraperitoneally injected with increasing doses of the A2A receptor agonist, 5′-(N-cyclopropyl)-carboxamido-adenosine (CPCA), and, for comparison, with the A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA). Both CPCA and CCPA were effective in suppressing generalized brainstem seizures with minimal effective concentrations of 2.5 and 1.5 mg/kg, respectively. Seizure suppression was maintained when CPCA was co-injected with the peripherally acting adenosine receptor antagonist 8-(p-sulphophenyl)theophylline, suggesting that central activation of A2A receptors effectively contributes to seizure suppression.