Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man |
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Authors: | P Karlsson G Sedvall C Halldin C -G Swahn L Farde |
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Institution: | (1) Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, S-17176 Stockholm, Sweden |
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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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Keywords: | Human brain D1-Dopamine receptors SCH 39166 Positron emission tomography Receptor occupancy |
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