Effects of Structural Modifications of N-CPM-Normorphine Derivatives on Agonist and Antagonist Activities in Isolated Organs
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.
KeywordsN-CPM-morphines opioid receptors isolated organs
Unable to display preview. Download preview PDF.
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.
- 2.Fürst, S., Friedmann, T., Knoll, J. (1988) Studies on the Interaction of Azidomorphine with Different Classes of Opiates. In: Regulatory Roles of Opioid Peptides. Springer-Verlag, pp. 358–377.Google Scholar
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.