Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations

Int J Rad Appl Instrum A. 1991;42(5):451-5. doi: 10.1016/0883-2889(91)90105-a.

Abstract

SCH 39166 [(-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo(d)naphtho-(2,1- b)azepine] is a new more selective dopamine D-1 receptor antagonist than the widely used SCH 23390. [11C]SCH 39166 was prepared by N-methylation of the desmethyl compound SCH 40853 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-5H- benzo(d)naphtho-(2,1-b)azepine] with [11C]methyl iodide. Reaction in acetone with subsequent straight-phase semi-preparative HPLC resulted in 20-30% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 35-40 min and a radiochemical purity greater than 99%. The specific activity obtained at EOS was about 1500 Ci/mmol (55 GBq/mumols). [11C]SCH 39166 was injected into a Cynomolgus monkey. PET-analysis demonstrated accumulation in the striatum, a region known to have a high density of dopamine D-1 receptors. In a displacement experiment, radioactivity in the striatum was markedly reduced after injection of 6 mg unlabelled SCH 23390, thus demonstrating the specificity and reversibility of [11C]SCH 39166 binding to dopamine D-1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzazepines / chemical synthesis*
  • Benzazepines / pharmacokinetics
  • Carbon Radioisotopes
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dopamine Antagonists*
  • Isotope Labeling
  • Ligands
  • Macaca fascicularis
  • Tomography, Emission-Computed*

Substances

  • Benzazepines
  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Ligands
  • ecopipam