Autoradiographic distribution of [3H]-suriclone binding sites in the rat brain

Suriclone is a potent non-benzodiazepine anxiolytic belonging to the cyclopyrrolone family. This study examines the distribution and properties of [³H]-suriclone binding sites in rat brain by autoradiography. The binding of [³H]-suriclone to rat brain sections was displaced completely by 1 m?M flumazenil; saturation experiments revealed a single class of binding sites with a K_D value of 1.19 nM and a Bmax of 1.05 pmol/mg protein. The pharmacological specificity of [³H]-suriclone binding was close to that of the benzodiazepine binding site on the GABA_A receptor. Unlike benzodiazepine (BZ) agonists, [³H]-suriclone binding to rat brain sections was not increased in the presence of GABA, and unlike imidazopyridines such as alpidem, suriclone was unable to discriminate between the BZ₁ and BZ₂ phenotype of the GABA_A receptor. The autoradiographic distribution of [³H]-suriclone binding sites in the rat brain was heterogeneous and relatively similar to that previously described for GABA_A receptors labelled by benzodiazepines; some regions, however, such as certain cortical areas, displayed a different labelling. The highest densities were found in frontal, occipital, parietal, and cingulate cortices (layers I, II, III, IV), in the molecular layer of the cerebellum, in the superior colliculus and in the hippocampus. Moderate binding densities appeared in numerous areas such as the inferior colliculus, the central grey, the dorsal raphé, and the hypothalamus whereas caudate putamen, globus pallidus, and thalamic nuclei displayed a low density of [³H]-suriclone binding sites. ©1995 Wiley-Liss, Inc.