Dopamine receptor occupancy in vivo: behavioral correlates using NNC-112, NNC-687 and NNC-756, new selective dopamine D1 receptor antagonists.
The ability of dopamine D2, mixed D1/D2 and selective D1 receptor antagonists, including NNC-112, NNC-687, NNC-756, to inhibit the in vivo binding of [3H]SCH 23390 or [3H]raclopride to dopamine receptors was studied in mice and rats. Furthermore, the dopamine-antagonistic effects of these drugs were also studied in various behavioral models. Significant levels of in vivo receptor blockade were required for antagonism of typical dopamine agonist-mediated behaviors. However, fewer D1 than D2 receptors had to be blocked to produce similar antagonistic effects. Thus, there may be a greater receptor reserve for D2 receptors than for D1 receptors.
Nielsen
E B
EB
Department of Behavioral Pharmacology, CNS Division, Novo Nordisk A/S, Måløv, Denmark.
Andersen
P H
PH
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D001552:Benzazepines; D001572:Benzofurans; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C077123:NNC 112; C077122:5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol; D000661:Amphetamine; D004298:Dopamine