Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations.
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.
Halldin
C
C
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
Farde
L
L
Barnett
A
A
Sedvall
G
G
D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D018492:Dopamine Antagonists; D007553:Isotope Labeling; D008024:Ligands; D008252:Macaca fascicularis; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D008024:Ligands; C058081:ecopipam