Activation of adenosine A₁ receptors underlies anticonvulsant effect of CGS21680

Focal injection of the adenosine A_2A receptor agonist CGS21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5′-N-ethyl-carboxamidoadenosine) in the rat prepiriform cortex produced a reduction in the severity of bicuculline methiodide-induced motor seizures. The anticonvulsant effect of CGS21680 exhibited dose-dependency and modest potency (ED₅₀=605±47 pmol/rat). Pharmacological characterization of the anticonvulsant response in the prepiriform cortex revealed a significant correlation between the potency of adenosine analogs as anticonvulsants and their respective affinities for adenosine A₁ receptors in vitro. These results indicate that the low affinity of CGS21680 for adenosine A₁ receptors is sufficient to account for the anticonvulsant activity of this compound in the rat prepiriform cortex.