Effects of orally vs. parenterally administrated trimebutine on gastrointestinal and colonic motility in dogs.
The influence of oral administration and intravenous infusion of trimebutine maleate (TMB) and N-desmethyl TMB (NDTMB), its main metabolite, was investigated in conscious dogs equipped with chronically implanted strain-gauges. In fasted dogs, TMB (10 to 20 mg/kg per os) delayed the occurrence of the next activity front on both stomach and duodenum by reinforcing the duration of the intestinal phase II. It also induced the occurrence of an additional migrating phase III. These effects were associated with a colonic stimulation generally followed by an inhibition. Comparatively NDTMB at similar dosages disrupted the antral cyclic phases which were replaced by continuous low amplitude contractions during 5-7 h. The MMC pattern persisted with a significant increase in the duration of phase II, and the colonic motility was inhibited during 4.3 to 6.7 h. Infused intravenously at a dose of 3 mg X kg-1 X h-1, TMB immediately inhibited the gastric cyclic contractions in fasted dogs. As for the oral route, the small bowel exhibited an increase in the duration of phase II frequently associated with the occurrence of an additional phase III. Furthermore an inhibition of the colonic motility was observed only at the end of the infusion and lasted at least 4 h. At similar dosage NDTMB had less pronounced inhibitory effects on gastric activity fronts and in contrast with TMB, the inhibitory effect on the colonic motility was observed as soon as the infusion of NDTMB started. These data demonstrate that orally administered TMB stimulates intestinal motility as previously described for i.v. route but in contrast to parenteral administration also stimulates antral and colonic motility.(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004386:Duodenum / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D007262:Infusions, Intravenous; D013997:Time Factors; D014287:Trimebutine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D001565:Benzoates; C053065:N-desmethyltrimebutine; D014287:Trimebutine