Differences of affinity ot 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 κ-opioid receptors in [3H]U-69593, a selective κ-receptor agonist. These results suggest that trimebutine, showing its low affinity to opioid receptors, possesses μ-receptor selective properties rather than those of κ-opioid receptor in the peripheral tissues and in the central brain homogenate.
https://www.jstage.jst.go.jp/article/bpb1978/13/7/13_7_448/_article