Koman A, Kolb V M, Terenius L
Department of Pharmaceutical Pharmacology, Uppsala University, Sweden.
Pharm Res. 1987 Apr;4(2):147-9. doi: 10.1023/a:1016475204694.
The interaction of naloxone estrone azine (N-EH) with various opioid receptor types was studied in vitro. Its potency as an antagonist of opioid effects was compared to that of naloxone on the electrically evoked contractions of mouse vas deferens (Mvd) and guinea pig ileum myenteric plexus longitudinal muscle (Gpi) preparations. N-EH was found to be 9-fold more potent than naloxone in antagonizing the effects of D-Ala2-Leu5-enkephalin in the Mvd and 22-fold less potent in antagonizing normorphine in the Gpi. In the Mvd, the recovery half-time for N-EH was longer than 1000 min. Neither compound showed agonism. The two compounds were also compared for their capacity to displace the binding of 3H-D-Ala2-Leu5-enkephalin, 3H-dihydromorphine, and 3H-ethylketocyclazocine to rat brain membranes under conditions where delta, mu, and kappa sites were labeled. The relative affinities were 0.70, 0.16, and 0.14 for N-EH and 0.05, 0.87, and 0.08 for naloxone, respectively. Thus, compared to naloxone, which is mu selective, N-EH is a delta-selective antagonist.
在体外研究了纳洛酮雌酮嗪（N-EH）与各种阿片受体类型的相互作用。将其作为阿片类效应拮抗剂的效力与纳洛酮对小鼠输精管（Mvd）电诱发收缩和豚鼠回肠肌间神经丛纵肌（Gpi）制剂的效力进行了比较。发现N-EH在拮抗Mvd中D-Ala2-Leu5-脑啡肽的作用方面比纳洛酮强9倍，而在拮抗Gpi中去甲吗啡的作用方面效力低22倍。在Mvd中，N-EH的恢复半衰期超过1000分钟。两种化合物均未表现出激动作用。还比较了这两种化合物在标记δ、μ和κ位点的条件下置换3H-D-Ala2-Leu5-脑啡肽、3H-二氢吗啡和3H-乙基酮环唑辛与大鼠脑膜结合的能力。N-EH的相对亲和力分别为0.70、0.16和0.14，纳洛酮的相对亲和力分别为0.05、0.87和0.08。因此，与具有μ选择性的纳洛酮相比，N-EH是一种δ选择性拮抗剂。
