Local actions of trimebutine maleate in canine small intestine

A study of the local actions of trimebutine (TMB) maleate and its N-diesmethyl metabolite (TMB-M) was carried out in the gastrointestinal tract of anesthetized dogs. In the unstimulated small intestine, but not in the stomach or colon, i.a. TMB and TMB-M caused activation of circular muscle. Like the activation by i.a. [Met5]-enkephalin, this was antagonized by naloxone. In field-stimulated segments of stomach and small intestine circular muscle, TMB or TMB-M, like dynorphin-1-13 or [Met5]-enkephalin, inhibited the phasic and tonic contractions which were mediated mostly by cholinergic, postganglionic nerves. However, the inhibitory effects of dynorphin-1-13 or [Met5]-enkephalin on small intestine were antagonized by naloxone whereas those of TMB sometimes or those of TMB-M usually were not. TMB or TMB-M did not affect responses to i.a. acetylcholine, but high doses reduced the contractile responses to subsequent field stimulation and excitatory responses to [Met5]-enkephalin. We concluded that the excitatory local actions of TMB or TMB-M on small intestine involved opioid receptors probably of the mu or delta types. Inhibitory local actions on nerve-mediated responses, however, may not have involved opioid receptors. Comparison of these data to results when TMB or TMB-M were given i.v. suggests that these agents also have peripheral actions to affect gastrointestinal motility at sites outside the gastrointestinal tract.