In vitro potency, affinity and agonist efficacy of highly selective delta opioid receptor ligands

T. H. Kramer, P. Davis, V. J. Hruby, T. F. Burks, F. Porreca

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56 Scopus citations


The purpose of these investigations was to estimate the relative potency, receptor affinity, and agonist efficacy of several selective delta opioid agonist peptides of diverse structure, including cyclic [D-Pen2,D- Pen5]enkephalin and its p-Phe4 halogen-substituted analogs, [D-Ser2-O- tBu,Leu5,Thr6]enkephalin. Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 (deltorphin I) and Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 (deltorphin II) in functional bioassays. The mouse-isolated vas deferens (MVD) and guinea pig-isolated ileum longitudinal muscle/myenteric plexus bioassay preparations were used; selectivity for delta opioid receptors was quantified by the relative agonist activity of the various peptides in the guinea pig-isolated ileum and MVD assays; agonist affinity and efficacy were determined using the technique of partial irreversible receptor inactivation in the MVD. Data from these experiments were analyzed both by the traditional null method and by use of the operational model of pharmacologic agonism; a comparison of these two methods, which were found to be similar, was performed. Potency determinations in MVD for the various peptides essentially matched those determined in other investigations; the relative affinity of the peptides correlated with the results of radioligand binding studies performed in other laboratories. The relative efficacies of the peptides studied were indistinguishable except for the peptide deltorphin I, which demonstrated efficacy several-fold lower than the remaining seven. All peptides were sufficiently efficacious to appear as full agonists under control conditions. These results suggest that the principle factor determining increases in potency of novel delta receptor ligands to date is an increase in receptor affinity. Efficacy should be incorporated as a drug design consideration for delta opioid agonists.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - 1993

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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