ADENOSINE-A1-RECEPTORS IN HUMAN HIPPOCAMPUS - INHIBITION OF [H-3] 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE BINDING BY ANTAGONIST DRUGS

Adenosine A1 receptors were visualized in human hippocampus using [H-3]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as a radioactive ligand probe. The receptor antagonists caffeine, the xanthine derivative KFM 19 and the carbamazepine analogue oxcarbazepine displaced [H-3]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). K(i)'s in the individual layers were in a range between 8.5 +/- 6.5 muM and 18.9 +/- 16.0 muM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. K(i)'s could not be calculated for oxcarbazepine as the IC50's were greater than 100 muM with estimated IC25'S Varying between 51.2 +/- 53.3 muM and 179.9 +/- 89.9 muM. Antagonism of endogenous adenosine at A1 receptors may thus explain part of the clinical effects of caffeine in humans and possibly exclusively the behavioral effects of KFM 19 in non-human primates.