TIME-COURSE OF 5-HT2A RECEPTOR OCCUPANCY IN THE HUMAN BRAIN AFTER A SINGLE ORAL DOSE OF THE PUTATIVE ANTIPSYCHOTIC DRUG MDL-100,907 MEASURED BY POSITRON EMISSION TOMOGRAPHY

MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin r eceptors. Animal studies suggest that MDL 100,907 may behave as an aty pical antipsychotic drug. Positron emission tomograph (PET) using [C-1 1]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. Afte r the baseline scan each subject was studied three times post dosing a t various time points. 5-HT2 occupancies were in the range of 70 and 9 0% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 Hours c ompared to the timepoint at 8 hours, when only 10 mg are administered (p < 0.05). Our results should allow determination of the appropriate dosing regimen for future trials in schizophrenic patients. (C) 1997 A merican College of Neuropsychopharmacology. Published by Elsevier Scie nce Inc.