4-[76Br]bromodexetimide and its inactive enantiomer 4-[76Br]bromolevetimide were prepared via electrophilic bromodesilylation using chloramine-T and no-carrier-added (NCA) [76Br]NH4. In vitro, Bmax measured on rat cortex membranes were 3.7 +/- 0.2 and < 0.07 pmol/mg protein for 4-[76Br]bromodexetimide and 4-[76Br]bromolevetimide, respectively. The kD of 4-[76Br]bromodexetimide was 1.9 +/- 0.3 nM. In vivo studies in rats showed specific uptake of 4-[76Br]bromodexetimide in cortex, striatum, thalamus and hippocampus. No specific uptake was observed with 4-[76Br]bromolevetimide. With [76Br]bromodexetimide, positron emission tomography (PET) studies in primates demonstrated a preferential accumulation of the radioactivity in the cortex and striatum which was displaced to the level of cerebellum by dexetimide. With 4-[76Br]bromolevetimide, the radioactivity concentrations in the cortex and striatum were similar to that of cerebellum.
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