INDUCTION OF PHASE-3 OF THE MIGRATING MOTOR COMPLEX IN HUMAN SMALL-INTESTINE BY TRIMEBUTINE

The effects of trimebutine, a drug used in the treatment of various gastrointestinal motility disorders, have been investigated in fed and fasted healthy subjects. Duodenojejunal motility was recorded manometrically with a 4-lumen probe. Trimebutine 50 or 100 mg was injected i.v. 3 or 25 min after observing a spontaneous Phase 3 complex in the fasted state. Other experiments were done in the postprandial state and after intravenous naloxone 0.8 mg. In the fasted state, trimebutine 100 mg, injected 25 min after a spontaneous Phase 3 complex consistently induced a premature Phase 3 complex. The mean duration of the migrating motor complex cycle decreased from 86.4 .+-. 10.8 min to 32.5 .+-. 1.0 min. Trimebutine 50 mg injected 3 and 25 min after a spontaneous Phase 3 complex did not significantly modify the periodicity of the migrating motor complex. Trimebutine 100 mg initiated Phase 3-like activity in the post-prandial state. Previous intravenous administration of naloxone 0.8 mg (Narcan) suppressed the stimulatory action of TMB. Thus, trimebutine is able to modify the motility pattern in the small intestine of man, possibly by acting at opioid receptors.