Dopamine receptor occupancy in vivo: behavioral correlates using NNC-112, NNC-687 and NNC-756, new selective dopamine D1 receptor antagonists

Eur J Pharmacol. 1992 Aug 14;219(1):35-44. doi: 10.1016/0014-2999(92)90577-q.

Abstract

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.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Benzazepines / metabolism
  • Benzazepines / pharmacology*
  • Benzofurans / pharmacology*
  • Catalepsy / chemically induced
  • Dopamine / metabolism*
  • Male
  • Mice
  • Motor Activity / drug effects
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, Dopamine D2 / drug effects
  • Stereotyped Behavior / drug effects

Substances

  • Benzazepines
  • Benzofurans
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • NNC 112
  • 5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol
  • Amphetamine
  • Dopamine