Trimebutine is an opioid receptor agonist.1,2,3 It binds to μ-, δ-, and κ-opioid receptors with Ki values of 0.34, 0.5, and 0.58 μM, respectively, in canine myenteric plexus synaptosomes.2 Trimebutine inhibits twitch contraction and acetylcholine (ACh) release induced by low-frequency electrical stimulation in isolated guinea pig longitudinal muscle with myenteric plexus (LM-MP; EC50s = 0.274 and 0.215 μM, respectively), effects that are inhibited by the opioid receptor antagonists naloxone and MR2266.3 It increases twitch contraction and ACh release induced by high-frequency electrical stimulation in isolated guinea pig LM-MP when used at concentrations of 1 μM or less, but inhibits these effects at 10 μM or more. Trimebutine (30, 100, and 300 μM) decreases the amplitude and frequency of spontaneous contractions in isolated guinea pig colonic smooth muscle strips.4 It also inhibits large conductance calcium-activated potassium (BKCa) and L-type calcium currents in colonic smooth muscle cells in a concentration-dependent manner.
1.Delvaux, M., and Wingate, D.Trimebutine: Mechanism of action, effects on gastrointestinal function and clinical resultsJ. Int. Med. Res.25(5)225-246(1997) 2.Allescher, H.D., Ahmad, S., and Daniel, E.E.Interaction of trimebutine and Jo-1196 (fedotozine) with opioid receptors in the canine ileumJ. Pharmacol. Exp. Ther.257(2)836-842(1991) 3.Taniyama, K., Sano, I., Taniyama, S., et al.Dual effect of trimebutine on contractility of the guinea pig ileum via the opioid receptorsGastroenterology101(6)1579-1587(1991) 4.Tan, W., Zhang, H., Luo, H.-S., et al.Effects of trimebutine maleate on colonic motility through Ca?+-activated K+ channels and L-type Ca?+ channelsArch. Pharm. Res.34(6)979-985(2011)