Effects of structural modifications of N-CPM-normorphine derivatives on agonist and antagonist activities in isolated organs

Riba, P. and Tóth, Z. and Hosztafi, S. and Friedmann, T. and Fürst, S. (2003) Effects of structural modifications of N-CPM-normorphine derivatives on agonist and antagonist activities in isolated organs. Acta Biologica Hungarica, 54 (2). pp. 177-181. ISSN 0236-5383

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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.

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