Action of trimebutine in cat and rabbit colon: evidence of an opioid-like effect.

Because trimebutine (TMB) is a drug that modulates colonic motility, we have attempted to determine the modifications of electrical activity underlying the motor effects of this drug. Experiments have been carried out on cat colon in vivo and on rabbit proximal colon in vivo and in vitro. The action of TMB (0.5-2 mg/kg in vivo; 10(-7) M-10(-6) M in vitro) consisted of an initiation or of an increase of spike potential activity that was unaffected by atropine (0.1 mg/kg for the cat, 2-3 mg/kg in vivo and 10(-6) M in vitro for the rabbit) and by hexamethonium (1.5 mg/kg for the cat and 2 mg/kg in vivo or 10(-6) M in vitro for the rabbit). In the cat under atropine, spike activity became cyclical, i.e., bursts of spikes were interrupted by periods of electrical silence. In the cat, TMB decreased the amplitude of excitatory junction potentials. Under atropine, TMB induced rhythmic variations in the amplitude of inhibitory junction potentials for 30 to 40 min. In the rabbit under TMB, excitatory junction potentials were enhanced whereas inhibitory junction potential amplitude was decreased. All the effects of TMB on spontaneous activity as well as on junction potentials are very similar to those observed in a previous work with morphine and enkephalins. The effects of TMB, unaffected by guanethidine, were antagonized by naloxone (2 mg/kg in vivo, 10(-6) M in vitro). These results suggest that opiate receptors, presumably located on intramural neurons, are involved in the effects of TMB.(ABSTRACT TRUNCATED AT 250 WORDS)