Schiller P W, Weltrowska G, Schmidt R, Berezowska I, Nguyen T M, Lemieux C, Chung N N, Carpenter K A, Wilkes B C
Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Que., Canada.
J Recept Signal Transduct Res. 1999 Jan-Jul;19(1-4):573-88. doi: 10.3109/10799899909036673.
The development of novel delta opioid antagonists and delta opioid agonists structurally derived from the prototype delta antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH), is reviewed. Both delta antagonists and delta agonists with extraordinary potency and unprecedented delta receptor selectivity were discovered. Some of them are already widely used as pharmacological tools and are also of interest as potential therapeutic agents for use in analgesia. The results of the performed structure-activity studies revealed that the delta antagonist versus delta agonist behavior of this class of compounds depended on very subtle structural differences in diverse locations of the molecule. These observations can be best explained with a receptor model involving a number of different inactive and active receptor conformations.
本文综述了新型δ阿片受体拮抗剂以及结构上源自原型δ拮抗剂TIPP（H-Tyr-Tic-Phe-Phe-OH）的δ阿片受体激动剂的研发情况。已发现了具有非凡效力和前所未有的δ受体选择性的δ拮抗剂和δ激动剂。其中一些已被广泛用作药理学工具，并且作为潜在的镇痛治疗药物也备受关注。所进行的构效关系研究结果表明，这类化合物的δ拮抗剂与δ激动剂行为取决于分子不同位置非常细微的结构差异。这些观察结果可以用涉及多种不同非活性和活性受体构象的受体模型来最好地解释。
