PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor

Psychopharmacology (Berl). 1993;113(2):149-56. doi: 10.1007/BF02245691.

Abstract

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with 11C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D1-dopamine receptors. This striatal uptake was displaced by high doses of the selective D1-antagonist SCH 23390 (2 mg/kg) but not by the 5HT2-antagonist ketanserin (1.5 mg/kg) or the selective D2-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [11C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [11C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24-28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [11C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [11C]NNC 756 the ratio was about 5. This ratio of 5 for [11C]NNC 756 is the highest obtained so far for PET radioligands for the D1-dopamine receptor.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Benzazepines / pharmacokinetics*
  • Benzazepines / pharmacology
  • Benzofurans / pharmacokinetics*
  • Brain / anatomy & histology
  • Brain Chemistry / drug effects
  • Carbon Isotopes
  • Chromatography, High Pressure Liquid
  • Dopamine Antagonists / pharmacokinetics*
  • Humans
  • Ligands
  • Macaca fascicularis
  • Male
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism*
  • Species Specificity
  • Tomography, Emission-Computed
  • Tomography, X-Ray Computed

Substances

  • Benzazepines
  • Benzofurans
  • Carbon Isotopes
  • Dopamine Antagonists
  • Ligands
  • Receptors, Dopamine D1
  • 5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol
  • odapipam