U-50,488, a selective kappa opioid agonist: comparison to other reputed kappa agonists.
1. U-50,488 is a structurally novel, non-mu opioid. In the present experiments it was compared to the reputed kappa opioid agonists, ketazocine, ethylketocyclazocine and bremazocine as regards analgesic cross tolerance to morphine and U-50,488, antagonism of analgesia by naloxone and MR-2266 (in vivo pA2 determination), and narcotic antagonist properties (antagonism of morphine analgesia and precipitation of abstinence in morphine-dependent mice). 2. The analgesic mechanism of bremazocine was similar to that of U-50,488 but the former compound had, in addition, considerable mu-antagonist activity. The analgesic mechanisms of the ketazocines were less selective; both shared both mu and kappa agonist properties. U-50, 488, however, had no such mu agonist or antagonist effects and thus is a more selective kappa agonist. 3. This compound and its congeners may prove useful in the elucidation of the functions of kappa receptors in the central nervous system.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa
D001575:Benzomorphans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine