BOC-Tyr-Pro-Gly-Phe-Leu-Thr(O1Bu) is a potent, highly δ-opioid receptor-selective competitive antagonist, the K(e) values in the mouse vas deferens in vitro assay against [D-Ala2, D-Leu5]-enkephalin, [D-Pen2, D- Pen5]enkephalin and deltorphin-II being 39.5, 38.7 and 27.3 nM, respectively, whereas those against [D-Ala2, MePhe4-Gly5-ol]enkephalin (DAMGO) and ethylketocyclazocine in the guinea-pig ileum are 368,000 and > 200,000 nM, giving a higher than 9000-fold δ- vs μ- and a higher than 5000- fold δ- vs κ-selectivity ratio. The K(i) values against various labeled δ- ligands in the rat brain receptor binding assay were in the 300-1000 nM range, whereas the K(i) against [3H]-DAMGO was higher than 30,000 nM. The striking discrepancies between bioassay and receptor binding data show another aspect of already recognized differences of mouse vas deferens and rat brain δ-receptors. With the aim of producing a δ-selective affinity ligand, we synthesized the BOC-Mel1 derivative; however, there was a 175- fold loss of δ-receptor affinity in the bioassay and no indication of an irreversible interaction, but a δ-agonist effect appeared in spite of nonprotonated nitrogen. The corresponding BOC-Phe1 derivative had a 10 times higher affinity and, apparently, no agonist activity.
|Number of pages||9|
|Journal||Archives internationales de pharmacodynamie et de therapie|
|Publication status||Published - Dec 1 1995|
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