BINDING PROFILE OF BENEXTRAMINE AT NEUROPEPTIDE-Y RECEPTOR SUBTYPES IN RAT-BRAIN AREAS

Binding studies in rat whole brain, frontoparietal cortex and brainste m membrane preparations revealed that benextramine displaced [H-3]neur opeptide Y specific binding from a low and a high affinity site with I C50 values in the mu M (36 +/- 2, 4.4 +/- 1.4 and 300 +/- 120 mu M, re spectively) and the pM (29.3 +/- 12.1, 0.35 +/- 0.11 and 0.42 +/- 0.03 pM, respectively) range, whereas in rat hippocampus benextramine disp laced [H-3]neuropeptide Y specific binding from one site only with an IC50 value of 22.8 +/- 5.7 mu M. With the exception of frontoparietal cortex binding assay, benextramine was not able to completely inhibit [H-3]neuropeptide Y specific binding revealing the presence of a benex tramine nonsensitive third binding site. Benextramine pretreatment fol lowed by membrane washing demonstrated that benextramine inhibited irr eversibly both high and low affinity sites.