Opioid antagonist properties of the highly δ-receptor-selective BOC- Tyr-Pro-Gly-Phe-Leu-Thr(O(t)Bu) peptide and of its Phe1 and Mel1 analogues

A. Z. Ronai, A. Magyar, G. Orosz, A. Borsodi, S. Benyhe, G. Toth, E. Mako, E. Katay, E. Babka, K. Medzihradszky

Research output: Contribution to journalArticle

8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)361-369
Number of pages9
JournalArchives internationales de pharmacodynamie et de therapie
Issue number3
Publication statusPublished - Dec 1 1995


ASJC Scopus subject areas

  • Pharmacology

Cite this