title: Partial agonistic effect of 9-hydroxycorynantheidine on mu-opioid receptor in the guinea-pig ileum.
abstract: 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 mu-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), (5alpha,7alpha,8beta)-(+)-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 mu-opioid receptor. 9-Hydroxycorynantheidine shifted the concentration-response curve for DAMGO slightly to the right. Pretreatment with the mu-opioid selective and irreversible antagonist beta-funaltorexamine hydrochloride (beta-FNA) shifted the concentration-response curve for DAMGO to the right without affecting the maximum response. On the other hand, beta-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 mu-opioid receptors in the guinea-pig ileum.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan. kenjiro@jiu.ac.jp
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takayama
authors.forename: Hayato
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Aimi
authors.forename: Dhavadee
authors.initials: D
authors.lastname: Ponglux
authors.forename: Kazuo
authors.initials: K
authors.lastname: Watanabe
authors.forename: Syunji
authors.initials: S
authors.lastname: Horie
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000819:agonists*; D046948:Secologanin Tryptamine Alkaloids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C510182:9-hydroxycorynantheidine; D026121:Indole Alkaloids; D017450:Receptors, Opioid, mu; D046948:Secologanin Tryptamine Alkaloids; C001801:mitragynine