Differential binding properties of oripavines at cloned μ- and δ-opioid receptors
Abstract
This study examines the possibility that oripavine opioid receptor agonists bind equally to both high and low affinity states of the mu-opioid receptor. Studies were performed in C6 cells expressing mu- or delta-opioid receptors; high and low agonist affinity states of the receptors were defined by the absence and presence, respectively of Na+ ions and the GTP analog Gpp(NH)p. At the mu-opioid receptor dihydroetorphine and etorphine were full agonists, buprenorphine had moderate efficacy while diprenorphine was an antagonist. At the delta-opioid receptor, dihydroetorphine, etorphine, and diprenorphine had moderate efficacy while buprenorphine was an antagonist. The binding affinities of the oripavines at the mu-opioid receptor decreased only one to 2-fold in the presence of NaCl and Gpp(NH)p. In contrast, decreases in oripavine affinity at the delta-opioid receptor correlated with delta-opioid receptor efficacy. The ability of oripavine agonists to bind with high affinity to the low agonist affinity state of the nu-opioid receptor may explain the high potencies of these compounds in vivo.
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Buprenorphine acts as a partial agonist at mu opioid receptors and an antagonist at kappa opioid receptors.
“Buprenorphine, a mu opioid receptor partial agonist (274-276) and a kappa opioid receptor antagonist (277)”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [275]
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A brain-centric model of suicidal behavior
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- Authors
- Lee, K. O., Akil, H., Woods, J. H., & Traynor, J. R.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Traynor, John R
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 378
- Issue
- 3
- Pages
- 323-330
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2068950095
- Cited by
- 117
- References
- 41
- Citations by year
- 2026: 2 · 2025: 2 · 2022: 1 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 7 · 2012: 2
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da002265-19)
- National Institute on Drug Abuse (DA-00254, DA02265)
- National Institute of General Medical Sciences (T32GM007767, GM-07767)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
- Keywords
- oripavine, mu-opioid receptor, delta opioid receptor, receptor binding affinity, Gpp(NH)p, dihydroetorphine, etorphine, buprenorphine, diprenorphine, opioid agonists
- MeSH terms
- Analgesics, Opioid, Animals, Benzamides, Binding, Competitive, Buprenorphine, Cloning, Molecular, Diprenorphine, Dose-Response Relationship, Drug, Etorphine, Fentanyl, Morphine, Naloxone, Piperazines, Radioligand Assay, Sulfur Radioisotopes, Thebaine, Tritium, Tumor Cells, Cultured, Guanosine 5'-O-(3-Thiotriphosphate), Receptors, Opioid, mu, Receptors, Opioid, delta, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Rats
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