EPILEPTOGENIC ACTIONS OF XANTHINES IN RELATION TO THEIR AFFINITIES FOR ADENOSINE A(1) RECEPTORS IN CA3 NEURONS OF HIPPOCAMPAL SLICES (GUINEA-PIG)

In order to analyze the epileptogenic mechanisms of caffeine and relat ed xanthines, putative effects of these drugs were studied on adenosin e receptors of CA3 neurons in hippocampal slices. Epileptogenic concen trations of different xanthine derivatives strongly correlated with th eir affinities for the inhibitory A1 adenosine receptor subtype. The A 1 receptor agonists adenosine and R-PIA reversibly depressed xanthine- induced epileptic activity without effects on the resting membrane pot ential or on spontaneously occurring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A1 receptors through an abnormal rise of intrac ellular cAMP and to the excessive transmembrane calcium fluxes underly ing paroxysmal depolarization shifts.