TENA, a selective kappa opioid receptor antagonist.
A number of opioid antagonists (TENA, naloxone, Mr 2266, WIN 44441) were evaluated for their selectivity in antagonizing the effect of mu, kappa, and delta agonists in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Among these four antagonists, TENA was the most potent and the only ligand which was selective for kappa receptors. In this regard TENA was approximately 27-times more effective in antagonizing the kappa agonist, U-50488H, relative to the mu agonist, morphine, and it was about 5-times more effective against ethylketazocine (EK) relative to morphine. At the same concentration (20 nM) TENA did not significantly antagonize the delta agonist, [D-Ala2,D-Ala5]enkephalin (DADLE), in the MVD. Also, TENA was more effective than naloxone, EK, or U-50488H in protecting kappa receptors from irreversible blockage by beta-CNA. The results of this study indicate that TENA is the most selective kappa antagonist yet reported.
Portoghese
P S
PS
Takemori
A E
AE
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D008297:Male; D051379:Mice; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014649:Vas Deferens / Q000378:metabolism
D001392:Azocines; D001575:Benzomorphans; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C027247:MR 2266; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C044564:6,6'-(ethylenebis(oxyethyleneimino))bis(17-cyclopropylmethyl)-4,5-epoxymorphinan-3,14-diol; D003496:Cyclazocine; C035969:quadazocine