PARAXANTHINE DISPLACES THE BINDING OF [H-3] SCH-23390 FROM RAT STRIATAL MEMBRANES

We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 μM; K(low) = 95.9 μM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 μM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 μM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioral stimulation produced by caffeine. © 1990.