In vivo opiate receptor binding of oripavines to mu, delta and kappa sites in rat brain as determined by an ex vivo labeling method

The relative in vivo receptor affinities of three oripavine drugs given subcutaneously were determined at the mu, delta and kappa type of opiate binding sites in rat brain. The oripavines include the agonist etorphine, the antagonist diprenorphine and the mixed agonist-antagonist buprenorphine. With the use of mu, delta and kappa specific labeling conditions in brain homogenates immediately after sacrifice (ex vivo labeling), the method relies on the assay of those receptor sites that remain unbound in vivo. Because of the slow receptor binding kinetics of the oripavines, little or no dissociation of the in vivo ligand occurs during the ex vivo labeling period. All three drugs displayed lower affinity in vivo at the delta sites relative to mu sites, whereas the kappa affinities were highly variable. Etorphine displayed considerable mu selectivity, while burpenorphine's affinity at the mu and kappa sites was similar. The apparent in vivo binding affinities obtained from the ex vivo labeling approach are compatible with previous results where tracers were applied in vivo. The dramatic differences of the in vivo and in vitro opiate receptor binding properties of the oripavines demonstrate the need for in vivo receptor binding parameters in the analysis of the function of individual receptor types.