title: Pharmacological characterization and positron emission tomography evaluation of 4-[76Br]bromodexetimide and 4-[76Br]bromolevetimide for investigations of central muscarinic cholinergic receptors.
abstract: 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.
authors.affiliation: Service Hospitalier Fédéric Joliot, Orsay, France.
authors.forename: C
authors.initials: C
authors.lastname: Loc'h
authors.forename: M
authors.initials: M
authors.lastname: Kassiou
authors.forename: V
authors.initials: V
authors.lastname: Strijckmans
authors.forename: M
authors.initials: M
authors.lastname: Bottlaender
authors.forename: A
authors.initials: A
authors.lastname: Katsifis
authors.forename: L
authors.initials: L
authors.lastname: Schmid
authors.forename: M
authors.initials: M
authors.lastname: Mazière
authors.forename: R M
authors.initials: RM
authors.lastname: Lambrecht
authors.forename: B
authors.initials: B
authors.lastname: Mazière
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001967:Bromine Radioisotopes / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D003909:Dexetimide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005625:Frontal Lobe / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D018727:Muscarinic Antagonists; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D001967:Bromine Radioisotopes; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C099688:4-bromodexetimide; D003909:Dexetimide