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Acta Biologica Hungarica

, Volume 54, Issue 2, pp 177–181 | Cite as

Effects of Structural Modifications of N-CPM-Normorphine Derivatives on Agonist and Antagonist Activities in Isolated Organs

  • P. Riba
  • Z. Tóth
  • S. Hosztafi
  • T. Friedmann
  • S. FürstEmail author
Article

Abstract

The agonistic and antagonistic properties of N-cyclopropylmethyl (N-CPM) morphine derivatives were observed in mouse vas deferens (MVD), longitudinal muscle of guinea pig ileum (GPI) and rabbit vas deferens (LVD). In MVD the Ke values of the titled compounds (N-CPM-morphine, N-CPM-isomorphine, N-CPM-dihydromorphine, N-CPM-dihydroisomorpPhine, N-CPM-dihydromorphone and naltrexone) were measured for μ, κ- and δ-receptors using normorphine, ethylketocyclazocine (EKC) and D-Pen2-D-Pen5-enkephaline (DPDPE) as selective agonists on the receptors, respectively. For μ-receptors of MVD the tested compounds showed similar affinity. For κ-receptors the non-iso-6-OH derivatives possessed much less affinity than the iso-derivatives. Similar difference could be observed for δ-receptors. The agonistic activities of these compounds in MVD were observed to be between 0–20% of the inhibition of muscle contractions. In GPI the compounds - except naltrexone - possessed strong agonistic activities effectively antagonized by nor-binaltorphimine (nor-BNI) (Ke of nor-BNI was 0.23 nM) suggesting that they were strong κ-receptor agonists. We investigated these agents in LVD too, which contains κ-receptors, but they did not produce any agonist potencies. It raises the possibility that the κ-receptor subtypes of LVD and MVD are different from the κ-receptor subtype of GPI or the vasa deferentia contain much fewer κ-receptors than GPI and the intrinsic activities of these compounds are too small to reach the 50% inhibition of the contractions.

Keywords

N-CPM-morphines opioid receptors isolated organs 

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Notes

Acknowledgments

We thank Mrs L. Papp for her excellent technical assistance. This work was supported by grants from OMFB (9748452); ETT 1-13/94; OTKA-T-017687 Hungary.

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Copyright information

© Akadémiai Kiadó, Budapest 2003

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • P. Riba
    • 1
  • Z. Tóth
    • 2
  • S. Hosztafi
    • 2
  • T. Friedmann
    • 1
  • S. Fürst
    • 1
    Email author
  1. 1.Department of PharmacologySemmelweis UniversityBudapestHungary
  2. 2.ICN Hungary Ltd.TiszavasváriHungary

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