BW373U86, its enantiomers, and related compounds: Interactions of non-peptide delta agonists at multiple δ_cx binding sites in rat brain

Previous studies delineated two classes of δ binding sites: a δ binding site not associated with the opioid receptor complex, termed the δ_ncx site, and a δ site associated with the opioid receptor complex, termed the δ_cx site (for review see (1)). More recent studies resolved two δ_cx binding sites in rat brain termed δ_cx-1 and δ_cx-2 (2). Pretreatment of membranes with the δ-selective acylating agent (+)-trans-SUPERFIT depletes membranes of the δ_ncx binding site which permits selective labeling of the δ_cx binding sites with [³H]DADLE (3). Ligand-selectivity studies of the non-peptide δ agonist, BW373U86, its enantiomers and related compounds showed that these drugs have higher affinities for δ sites than μ sites (4,5). This study determined the selectivity of these compounds for the two δ_cx binding sites. The data indicate that (+)-4-[(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) and deltorphin-II are highly selective for δ_cx-2 binding site (2758-fold and 700-fold respectively). In contrast, morphine is selective for δ_cx-1 binding site (78-fold).