The binding to rat brain homogenates of Mr2034, a universal opiate.
Mr2034 has been proposed as a kappa opiate. While Mr2034 inhibited the binding of the kappa opiate 3H-ethylketocyclazocine better than unlabeled ethylketocyclazocine, it also displaced the binding of 3H-dihydromorphine and 3H-SKF 10047 more potently than morphine and SKF 10047, respectively. 3H-D-ala2-D-leu5-enkephalin was displaced equally well by Mr2034 and D-ala2-D-leu5-enkephalin. Saturation studies of 3H-Mr2034 binding demonstrated curvilinear Scatchard plots which could be dissected into two components by computer: KD1 0.06 nM, Bmax1 2.49 fmoles/mg tissue; and KD2 2.4 nM, Bmax2 6.57 fmoles/mg tissue. A portion of the higher affinity (KD 0.06 nM) component was inhibited by naloxonazine treatment in vitro (50 nM), suggesting that 3H-Mr2034 bound with very high affinity to mu1 sites. Displacement of 3H-Mr2034 binding by opioids was multiphasic, again implying that 3H-Mr2034 was binding to more than one class, of site. In view of its similar potency in inhibiting mu (3H-dihydromorphine), kappa (3H-ethylketocycla-zocine), sigma (3H-SKF 10047) and delta (3H-D-ala2-D-leu5-enkephalin) opioids Mr2034 might be considered a universal opiate.
D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D008297:Male; D009019:Morphinans / Q000378:metabolism*; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D001575:Benzomorphans; D009019:Morphinans; D011957:Receptors, Opioid; D009270:Naloxone; C032478:MR 2034; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C012134:SK&F 10047; C034643:naloxonazine; D004090:Dihydromorphine; D010620:Phenazocine; D003496:Cyclazocine