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.
Duffy
R A
RA
Schering-Plough Research, Bloomfield, NJ 07003.
Kaminska
G
G
Chipkin
R E
RE
McQuade
R D
RD
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists; D005260:Female; D008253:Macaca mulatta; D008297:Male; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015854:Up-Regulation / Q000187:drug effects*
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C058081:ecopipam