Effect of a new Colonic Prokinetic Compound, T-1815, on Gastrointestinal Motility in Anesthetized and Conscious Fasted Dogs.

Abstract

Effect of T-1815, a new colonic prokinetic compound, on gastrointestinal motility was studied in anesthetized and conscious dogs fasted for 24 hr before experiment.In anesthetized dogs, intravenous injection of T-1815 in doses of 0.3-3.0 mg/kg caused a biphasic effect on the gastric motility, a slight decrease followed by a slight increase. While the compound elicited only an increase in motility of the duodenum, jejunum and colon. In the colon, high- From the above results, it is concluded that the pharmacological effect of T-1815 on gastrointestinal motility is different from that of the cholinergic agonist. In addition, T-1815 seems to have a characteristic to induce high-amplitude contractions which are known to be closely related to defecation.

Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans

“…Bethanechol (Urecholine; Merck, West Point, PA) was administered at a dose of 2.5, 5, or 10 mg subcutaneously, because intravenous administration is contraindicated in humans. Prior studies in humans demonstrated that these doses are safe, enhance bladder contractility (21), and encompass the dose (0.05 mg/kg sc) that increased colonic motor activity in dogs (33). The subcutaneous dose used clinically to relieve postoperative ileus and abdominal distension is 5 mg (28,29).…”