One aspect of opiates a lot of people don't know about is their effect on the GI. They slow gut motility, so opiate abusers often experience constipation (and diarrhea upon withdrawal). Opium used to be used medically as an antidiarrheal medication in a tincture with camphor - paregoric. Interestingly, opiates are still available OTC for the treatment of diarrhea.
Loperamide is unique among medically used opiates in that it isn't CNS-active - so you get the gut-slowing effects, without pain relief or addictive potential. It's the only opiate you can get OTC in most markets.
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So...the use of loperamide in medicine has always made me wonder about the potential for an opioid antagonist that does not cross the BBB to treat constipation. I don't know if this is feasible... I am not sure to what extent the opioid peptides in the bowels control GI motility (and thus constipation) but it would be interesting to know!!
I read an anecdote from a pharmacy intern who expressed concern that her employers were using a bottle of paregoric as a doorstop. The pharmacist on duty said, "Oh, don't worry; nobody knows what paregoric is anymore." The intern said, "Anyone who's read William S. Burroughs knows what paregoric is." Five minutes later, a breeze blew the door closed, and the paregoric was nowhere to be found.
Yah, because Burroughs made opiate use sound sooooo much fun! But seriously....do they still make paregoric? (Literally, tummy opium)
Is that a methadone analogue then? The left side of the molecule certainly bears a superficial resemblance, while the right side is no doubt the functional group that keeps it from being psychoactive...