Selective up-regulation of D-1 dopamine receptors following chronic administration of SCH 39166 in primates.

Caudate, putamen and frontal cortex tissues were obtained from rhesus monkeys that had taken part in a toxicology study required by the Food and Drug Administration. These monkeys had received daily oral treatments of SCH 39166 at three different doses (3, 12 and 48 mg/kg) for three consecutive months. Plasma membranes from the caudate and putamen were analyzed for changes in D-1 and D-2 receptor affinity and number using saturation analyses of 3H-SCH 23390 and 3H-spiperone binding, respectively. Saturation studies were performed on membranes from the frontal cortex using 3H-ketanserin to determine if 5HT2 receptor number or affinity were affected by chronic treatment with SCH 39166. Results indicate a significant, dose-dependent up-regulation of D-1 receptor number in both caudate and putamen, with no changes in either D-2 receptors in the striatal regions or 5HT2 receptors in the frontal cortex. These data, therefore, indicate that SCH 39166 is a selective antagonist at D-1 receptors in the CNS of nonhuman primates.