Identification of opiate/receptor binding in vivo.

The displacement of small amounts of tritiumlabbelled antagonists or agonists by increasing amounts of unlabelled antagonists in mouse brain in vivo offered the possibility of characterizing properties of opiate receptors in the intact animal. The displacement effect was stereospecific, saturable and dependent upon the affinity of the substance investigated. At brain concentrations of 0.3 nM, 75% of 3H-diprenorphine, 60% of 3H-naltrexone and 50% of 3H-naloxone were displaced by high amounts of the respective unlabelled drug. Comparison of the in vivo data with receptor binding in vitro revealed similar results in respect to binding sites and receptor affinity. The displacement was different in various brain areas. The time course of the displacement was also different for the various substances used and seems to reflect differences in the speed of association and dissociation to and from the receptors. The displacement of 3H-etorphine by naltrexone could be correlated with the reversal of analgesia.