Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man.

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 with 11C, 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.

• Authors: P Karlsson, G Sedvall, C Halldin, C G Swahn, L Farde
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 121 Issue 3 Pg. 300-8 (Oct 1995) ISSN: 0033-3158 [Print] Germany
• PMID: 8584610 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzazepines
• Dopamine Antagonists
• Receptors, Dopamine D1
• ecopipam

Topics

• Adult
• Benzazepines (adverse effects, pharmacokinetics, pharmacology)
• Binding, Competitive
• Brain (drug effects)
• Dopamine Antagonists (adverse effects, pharmacokinetics, pharmacology)
• Humans
• Male
• Radioligand Assay
• Receptors, Dopamine D1 (antagonists & inhibitors)
• Time Factors
• Tomography, Emission-Computed