I thought you might be interested in this potential future )next few years with Phase III and IV hopefully upcoming. J-113397 is a compound that is an agonist at a set of subreceptors callled the ORL-1 receptors (Opiate like receptor-1) recently discovered around 10 years ago where there purpose wasn't really understood. It' natural ligand is something called nociceptin. Here's the interesting part: Mice that had the gene for this receptor knocked out did not develop any tolerance to standard biomedical addiction protocol (3 days or 7 days continuous and increasing morphine admininstration). A few years later a research group prepared an exogeneous ligand (J-113397) and the researchers found, I believe, (I don't have the paper in front of me, its in the journal Pain, I believe, but a google search will bring you to the relevant paper (published in 2005 or 6, I believe, I can't link it becasue of my uni suscription licensces even with VPN) Main point: some mice were given steady doses of morphine while taking J----, along wiht control mice. They found virtulally no withdrawal syptoms on naloxone administration in this groupl. It's not our holy grail though as the standart J---- dose did not completely attenuate addiction/tolerance amongst mice who were given irregular increasing and lowering doses, though it did have some effect. If this work progresses I know what I will be doing after the phd. Vax, chem, lev, have you heard about these studies? I'm sure you guys probably have access to the literature at your schools.
Oh sorry, there's work in the Pain Journal but this specific article is as follows: The Journal of Pharmocology and Experimental Therapeutics, 2006, 318(1), 262-267. I believe the PI's name is RK Reinscheid. It's pretty interesting, especially considering it seems pretty cutting edge. (I USTFE and no one has mentioned J-113397), Imagine the freaking possilbilities of a total downstream tolerance/addiction modulator.:cool: