alpha(2)-Adrenoceptor subtypes in the human brain: A pharmacological delineation of [H-3]RX-821002 binding to membranes and tissue sections

In order to study the characterization and localization of [H-3]RX-821002 (2-methoxy-idazoxan) binding to alpha(2)-adrenoceptor subtypes in several regions of the human brain, we have carried out competition studies using both autoradiography and membrane binding assays. The alpha(2A)-adrenoceptor subtype was found to be predominant in the different layers of the frontal cortex, cerebellum and hippocampal formation, while in the neostriatum it was the non-alpha(2A)- (alpha(2B)- and alpha(2C)-) adrenoceptor subtype. In the frontal cortex, in addition to binding to the alpha(2A)-adrenoceptor subtype, [H-3]RX-821002 bound also to a small portion of alpha(2B)- and alpha(2C)-adrenoceptors in layer III, and labelled in the dentate gyrus and the CA(1) field, together with 5-HT1A receptors. 5-HT1A receptors were labelled predominantly in the stratum pyramidale layer. These results, in addition to delineate the relative presence of alpha(2)-adrenoceptor subtypes, indicate that caution is needed when analyzing RX 821002 binding to human brain tissue.