ORL1 agonists look promising for the treatment of neuropathic pain and also enhance mu-agonists and the rewarding nature of cocaine (the last point sort of inferring the link between the first 2).
Anyone care to perform an mm2-minimized overlay of:
and the (S) isomer of compound XIX in this paper:
Note that the piperidine nitrogen of the former overlays the amide nitrogen of the latter. The latter, BTW, is 3.5x the potency of etonitazene (which is x60 in humans, not the x1500 in mice that people think applies).
I honestly don't think anybody ever looked at the ORL1 affinity in older high-potency agonists. Nothing to patent, I guess.