New developments of the μ-selective opioid 3,8-diazabicyclo[3.2.1]octanes

Abstract

BW 373U86 is a novel, non-peptidic δ-opioid receptor ligand with agonist properties in mouse brain and in the mouse isolated vas deferens. The sensitivity of BW 373U86, and of the peptidic δ-opioid agonists [d-Pen2, D-Pen5]enkephalin (DPDPE) and [d-Ala2,Glu4]deltorphin, to regulation by guanine nucleotides and sodium was evaluated in competition studies against the 5 selective radioligand [3H]naltrindole. The IC50 values for DPDPE and [d-Ala2,Glu4]deltorphin were significantly increased in brain and mouse vas deferens in the presence of Gpp(NH)p and NaCl. In contrast, the IC50 values for BW 373U86 were not altered in the presence of Gpp(NH)p and NaCl in either tissue. The data indicate that the agonist properties of BW 373U86 may not be affected by the supposed uncoupling of the α-subunit of the G-protein from a receptor thought to be G-protein linked.