Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1976 Nov;73(11):4215–4219. doi: 10.1073/pnas.73.11.4215

The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists.

A P Feinberg, I Creese, S H Snyder
PMCID: PMC431391  PMID: 186791

Abstract

A model of the opiate receptor is proposed which explains structure-activity relationships of opiate drugs, including (i) the unique potency of certain opiates such as etonitazene, fentanyl, phenazocine, and oripavines; (ii) the role of N-allyl substituents in conferring antagonist properties; and (iii) chemical features that afford "pure" antagonists. The model indicates mlecular mechanisms for interconversion of the opiate receptor between respective states that bind agonists or antagonists with high affinity.

Full text

PDF
4215

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albertson N. F. Effect of 9-hydroxylation on benzomorphan antagonist activity. J Med Chem. 1975 Jun;18(6):619–621. doi: 10.1021/jm00240a019. [DOI] [PubMed] [Google Scholar]
  2. BECKETT A. H., CASY A. F. Synthetic analgesics: stereochemical considerations. J Pharm Pharmacol. 1954 Dec;6(12):986–1001. doi: 10.1111/j.2042-7158.1954.tb11033.x. [DOI] [PubMed] [Google Scholar]
  3. BESENDORF H., PELLMONT B., BACHTOLD H. P., REBER K., STUDER A. [On a tetrahydroisoquinoline compound with analgesic action]. Experientia. 1962 Oct 15;18:446–447. doi: 10.1007/BF02175848. [DOI] [PubMed] [Google Scholar]
  4. Hughes J. Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res. 1975 May 2;88(2):295–308. doi: 10.1016/0006-8993(75)90391-1. [DOI] [PubMed] [Google Scholar]
  5. Hughes J., Smith T. W., Kosterlitz H. W., Fothergill L. A., Morgan B. A., Morris H. R. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature. 1975 Dec 18;258(5536):577–580. doi: 10.1038/258577a0. [DOI] [PubMed] [Google Scholar]
  6. Hughes J., Smith T., Morgan B., Fothergill L. Purification and properties of enkephalin - the possible endogenous ligand for the morphine receptor. Life Sci. 1975 Jun 15;16(12):1753–1758. doi: 10.1016/0024-3205(75)90268-4. [DOI] [PubMed] [Google Scholar]
  7. Loew G. H., Berkowitz D. S. Quantum chemical studies of morphine-like opiate narcotics. Effect of N-substituent variations. J Med Chem. 1975 Jul;18(7):656–662. doi: 10.1021/jm00241a002. [DOI] [PubMed] [Google Scholar]
  8. Ong H. H., O-Ishi T., May E. L. Phenylmorphan agonists-antagonists. J Med Chem. 1974 Jan;17(1):133–134. doi: 10.1021/jm00247a026. [DOI] [PubMed] [Google Scholar]
  9. Pasternak G. W., Goodman R., Snyder S. H. An endogenous morphine-like factor in mammalian brain. Life Sci. 1975 Jun 15;16(12):1765–1769. doi: 10.1016/0024-3205(75)90270-2. [DOI] [PubMed] [Google Scholar]
  10. Pasternak G. W., Snowman A. M., Snyder S. H. Selective enhancement of [3H]opiate agonist binding by divalent cations. Mol Pharmacol. 1975 Nov;11(6):735–744. [PubMed] [Google Scholar]
  11. Pert C. B., Pasternak G., Snyder S. H. Opiate agonists and antagonists discriminated by receptor binding in brain. Science. 1973 Dec 28;182(4119):1359–1361. doi: 10.1126/science.182.4119.1359. [DOI] [PubMed] [Google Scholar]
  12. Perutz M. F. Stereochemistry of cooperative effects in haemoglobin. Nature. 1970 Nov 21;228(5273):726–739. doi: 10.1038/228726a0. [DOI] [PubMed] [Google Scholar]
  13. Perutz M. F., TenEyck L. F. Stereochemistry of cooperative effects in hemoglobin. Cold Spring Harb Symp Quant Biol. 1972;36:295–310. doi: 10.1101/sqb.1972.036.01.040. [DOI] [PubMed] [Google Scholar]
  14. Portoghese P. S. Stereochemical factors and receptor interactions associated with narcotic analgesics. J Pharm Sci. 1966 Sep;55(9):865–887. doi: 10.1002/jps.2600550902. [DOI] [PubMed] [Google Scholar]
  15. TPERENIUS L., Wahlström A. Morphine-like ligand for opiate receptors in human CSF. Life Sci. 1975 Jun 15;16(12):1759–1764. doi: 10.1016/0024-3205(75)90269-6. [DOI] [PubMed] [Google Scholar]
  16. Takeda M., Konda M., Inoue H., Saito S., Kugita H. Antagonists in the homobenzomorphan series. Adv Biochem Psychopharmacol. 1973;8(0):113–121. [PubMed] [Google Scholar]
  17. Wilson R. S., Rogers M. E., Pert C. B., Snyder S. H. Homologous N-alkylnorketobemidones. Correlation of receptor binding with analgesic potency. J Med Chem. 1975 Mar;18(3):240–242. doi: 10.1021/jm00237a003. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES