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

Suricloneis a potent non- benzodiazepine anxiolyticbelonging to the cyclopyrrolonefamily. This study examines the distribution and properties of [3H]- suriclone binding sitesin rat brain by autoradiography. The binding of [3H]- suricloneto rat brain sections was displaced completely by 1 mM flumazenil; saturation experiments revealed a single class of binding siteswith a KD value of 1.19 nM and a Bmax of 1.05 pmol/mg protein. The pharmacological specificity of [3H]- suriclonebinding was close to that of the benzodiazepine binding siteon the GABAA receptor. Unlike benzodiazepine(BZ) agonists, [3H]- suriclonebinding to rat brain sections was not increased in the presence of GABA, and unlike imidazopyridinessuch as alpidem, suriclonewas unable to discriminate between the BZ1 and BZ2 phenotype of the GABAA receptor. The autoradiographicdistribution of [3H]- suriclone binding sitesin the rat brain was heterogeneous and relatively similar to that previously described for GABAA receptorslabelled 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 colliculusand in the hippocampus. Moderate binding densities appeared in numerous areas such as the inferior colliculus, the central grey, the dorsal raphe, and the hypothalamus whereas caudate putamen, globus pallidus, and thalamic nuclei displayed a low density of [3H]- suriclone binding sites. ©1995 Wiley-Liss, Inc.