Adenosine A1 receptors in human hippocampus: inhibition of [3H]8-cyclopentyl-1,3-dipropylxanthine binding by antagonist drugs.
Adenosine A1 receptors were visualized in human hippocampus using [3H]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 [3H]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). Ki's in the individual layers were in a range between 8.5 +/- 6.5 microM and 18.9 +/- 16.0 microM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. Ki's could not be calculated for oxcarbazepine as the IC50's were greater than 100 microM with estimated IC25's varying between 51.2 +/- 53.3 microM and 179.9 +/- 89.9 microM. 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.
Deckert
J
J
Department for Neurochemistry, University of Würzburg, FRG.
Berger
W
W
Kleopa
K
K
Heckers
S
S
Ransmayr
G
G
Heinsen
H
H
Beckmann
H
H
Riederer
P
P
D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive; D002110:Caffeine / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism* / Q000494:pharmacology*
D000927:Anticonvulsants; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014970:Xanthines; C080664:KFM 19; D002220:Carbamazepine; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000078330:Oxcarbazepine