PHARMACOLOGICAL CHARACTERIZATION AND POSITRON EMISSION TOMOGRAPHY-EVALUATION OF 4-[BR-76]BROMODEXETIMIDE AND 4-[BR-76]BROMOLEVETIMIDE FOR INVESTIGATIONS OF CENTRAL MUSCARINIC CHOLINERGIC RECEPTORS

4-[Br-76]bromodexetimide and its inactive enantiomer 4-[Br-76]bromolev etimide were prepared via electrophilic bromodesilylation using chlora mine-T and no-carrier added (NCA) [Br-76]NH4. In vitro, B-max measured on rat cortex membranes were 3.7 +/- 0.2 and <0.07 pmol/mg protein fo r 4-[Br-76]bromodexetimide and 4 [Br-76]bromolevetimide, respectively. The k(D) of 4-[Br-76]bromodexetimide was 1.9 +/- 0.3 nM. In vivo stud ies in rats showed specific uptake of 4-[Br-76]bromodexetimide in cort ex, striatum, thalamus and hippo campus. No specific uptake was observ ed with 4-[Br-76]bromolevetimide. With [Br-76] bromodexetimide, positr on emission tomography (PET) studies in primates demonstrated a prefer ential accumulation of the radioactivity in the cortex and striatum wh ich was displaced to the level of cerebellum by dexetimide. With 4-[Br -76]bromolevetimide, the radioactivity concentrations in the cortex an d striatum were similar to that of cerebellum.