title: The opioid receptor selectivity for trimebutine in isolated tissues experiments and receptor binding studies.
abstract: Differences of affinity to and selectivity for trimebutine between peripheral and central opioid receptors have been investigated. Trimebutine inhibited electrically induced contraction of guinea-pig ileum (GPI) and mouse vas deferens (MVD) but not of rabbit vas deferens, and the inhibition was antagonized by naloxone and, to lesser extent, by nor-binaltorphimine (nor-BNI). The pA2 values for morphine and trimebutine with naloxone were higher than the values for these compounds with nor-BNI in both GPI and MVD preparations. GPI preparations incubated with a high concentration of morphine or trimebutine developed tolerance; however, there was no cross-tolerance between them, suggesting difference in the underlying mechanisms. In mouse and guinea-pig brain homogenate trimebutine was about 1/13 as potent as morphine to displace the [3H]naloxone binding, while it has no appreciable affinity for kappa-opioid receptors in [3H]U-69593, a selective kappa-receptor agonist. These results suggest that trimebutine, showing its low affinity to opioid receptors, possesses mu-receptor selective properties rather than those of kappa-opioid receptor in the peripheral tissues and in the central brain homogenate.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kaneto
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009020:Morphine / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000378:metabolism / Q000502:physiology*; D014287:Trimebutine / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
chemical_list: D011957:Receptors, Opioid; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; D014287:Trimebutine