Partial agonistic effect of 9-hydroxycorynantheidine on μ-opioid receptor in the guinea-pig ileum
Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa that is reported to have opioid agonistic properties. The 9-demethyl analogue of mitragynine, 9-hydroxycorynantheidine, is synthesized from mitragynine. 9-Hydroxycorynantheidine inhibited electrically stimula...
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Veröffentlicht in: | Life sciences (1973) 2006-04, Vol.78 (19), p.2265-2271 |
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Sprache: | eng |
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Zusammenfassung: | Mitragynine is an indole alkaloid isolated from the Thai medicinal plant
Mitragyna speciosa that is reported to have opioid agonistic properties. The 9-demethyl analogue of mitragynine, 9-hydroxycorynantheidine, is synthesized from mitragynine. 9-Hydroxycorynantheidine inhibited electrically stimulated guinea-pig ileum contraction, but its maximum inhibition was weaker than that of mitragynine and its effect was antagonized by naloxone, suggesting that 9-hydroxycorynantheidine possesses partial agonist properties on opioid receptors. Receptor binding assays revealed that 9-hydroxycorynantheidine has high affinity for μ-opioid receptors. In an assay of the guinea-pig ileum, naloxone shifted the concentration-response curves for [
d-Ala
2,
N-MePhe
4, Gly-ol
5]-enkephalin (DAMGO), (5α,7α,8β)-(+)
-N-Methyl-
N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U69593) and 9-hydroxycorynantheidine to the right in a competitive manner. The pA
2 values of naloxone against 9-hydroxycorynantheidine and DAMGO were very similar, but not that against U69593. As indicated by the two assay systems, the opioid effect of 9-hydroxycorynantheidine is selective for the μ-opioid receptor. 9-Hydroxycorynantheidine shifted the concentration–response curve for DAMGO slightly to the right. Pretreatment with the μ-opioid selective and irreversible antagonist β-funaltorexamine hydrochloride (β-FNA) shifted the concentration–response curve for DAMGO to the right without affecting the maximum response. On the other hand, β-FNA did not affect the curve for 9-hydroxycorynantheidine, but decreased the maximum response because of the lack of spare receptors. These studies suggest that 9-hydroxycorynantheidine has partial agonist properties on μ-opioid receptors in the guinea-pig ileum. |
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ISSN: | 0024-3205 1879-0631 |
DOI: | 10.1016/j.lfs.2005.09.030 |