Abstract
SCH 39166 is the first selective D1-dopamine receptor antagonist developed for clinical trials in schizophrenia. SCH 39166 was evaluated as a radioligand for PET, labeled with11C, and as a D1-dopamine receptor antagonist after single oral doses in healthy men. After intravenous injection of [11C]SCH 39166 distribution of radioactivity in brain grossly reflected D1-dopamine receptor density. The putamen to cerebellum ratio at equilibrium was low (1.54±0.18 SD), which makes [11C]SCH 39166 less suitable as a radioligand for applied PET studies. Saturability of specific binding was demonstrated after IV injection of [11C]SCH 39166 with low specific radioactivity. Stereospecificity of binding was examined using the stereoisomer [11C]SCH 39165. D1-Receptor occupancy was demonstrated with [11C]SCH 39166 2 h after administration of single oral doses of unlabeled SCH 39166 to each of three healthy subjects (25, 100 and 400 mg). There was a substantial reduction of specific [11C]SCH 39166 uptake in the putamen after all doses. Single oral doses of 100 mg induced approximately 70% D1-dopamine receptor occupancy in the basal ganglia, which should be sufficient to investigate the antipsychotic potential of D1-dopamine receptor antagonism in clinical studies.
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Karlsson, P., Sedvall, G., Halldin, C. et al. Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man. Psychopharmacology 121, 300–308 (1995). https://doi.org/10.1007/BF02246067
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DOI: https://doi.org/10.1007/BF02246067