Binding of [H-3](+)-BW373U86 to delta-opioid receptors in rat brain membranes

A tritiated form of the non-peptidic delta-opioid receptor agonist(+)-BW373U86 ((+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide) was synthesized and its binding characteristics studied. [H-3](+)-BW373U86 bound with subnanomolar affinity to rat brain membranes and was displaced most effectively by ligands selective for delta-opioid receptors. Naltrindole, naltriben, and 7-benzylidenenaltrexone exhibited apparent inhibition constants of 0.06, 1.54, and 4.49 nM, respectively, while mu- Or kappa-selective ligands showed little affinity for this site. [H-3](+)-BW373U86 binding was sensitive to the presence of guanine nucleotides; GDP caused a 3-fold decrease and 5'-guanylyl-imidodiphosphate (Gpp[NH]p) caused a 25% increase in binding affinity.