3H-SKF10047 receptor binding studies. Attempts to define the opioid sigma receptor

The results of experiments are described in which attempts have been made to use the multi-site ligand (d,l)3H-SKF10047 to define a binding site that may be the opioid sigma site. This was attempted by using highly selective blocking agents to eliminate binding at the other opioid sites. The remaining bound 3H-SKF10047, approximately 20% of total specific bound, was then characterized using competitive binding studies with different types of opioids. Under these conditions, a binding site was identified which is highly selective for the benzmorphans and certain morphinans known to cause dysphoria. The kappa selective agent (l)U-50488 did not demonstrate high activity for this site and neither did several mu opioids, PCP or the (d) enantiomers of two opioid benzmorphans. The carefully defined site may be the putative opioid sigma receptor.