Johnson N, Pasternak G W
Life Sci. 1983 Sep 5;33(10):985-91. doi: 10.1016/0024-3205(83)90755-5.
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.
Mr2034被认为是一种κ阿片受体激动剂。虽然Mr2034比未标记的乙基酮环唑新更能抑制κ阿片受体与3H-乙基酮环唑新的结合，但它分别比吗啡和SKF 10047更有效地取代了3H-二氢吗啡和3H-SKF 10047的结合。Mr2034和D-丙氨酸2-D-亮氨酸5-脑啡肽对3H-D-丙氨酸2-D-亮氨酸5-脑啡肽的取代效果相同。3H-Mr2034结合的饱和研究显示出曲线型Scatchard图，通过计算机可将其分解为两个成分：KD1为0.06 nM，Bmax1为2.49 fmol/mg组织；KD2为2.4 nM，Bmax2为6.57 fmol/mg组织。体外纳洛酮嗪处理（50 nM）可抑制一部分高亲和力（KD为0.06 nM）成分，这表明3H-Mr2034以非常高的亲和力与μ1位点结合。阿片类药物对3H-Mr2034结合的取代是多相的，这再次表明3H-Mr2034与不止一类位点结合。鉴于Mr2034在抑制μ（3H-二氢吗啡）、κ（3H-乙基酮环唑新）、σ（3H-SKF 10047）和δ（3H-D-丙氨酸2-D-亮氨酸5-脑啡肽）阿片受体方面具有相似的效力，Mr2034可能被视为一种通用的阿片受体激动剂。
