Effect of a new Colonic Prokinetic Compound, T-1815, on Gastrointestinal Motility in Anesthetized and Conscious Fasted Dogs.
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概要
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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-amplitude contractions were observed in 2 out of 5 animals at 1 mg/kg, i.v. of T-1815 and 4 out of 5 animals at 3 mg/kg. Bethanechol at 0.01 mg/kg, i.v. produced only a potentiation of the motility in all of the sites, but never induced high-amplitude contractions in the colon. During the interdigestive state in conscious dogs, intravenous T-1815 at 1 and 3 mg/kg caused contractions similar to the interdigestive phase III contractions at the stomach and duodenum in only 2 out of 7 experiments, and colonic motility was slightly depressed at 3 mg/kg. Oral administration of T-1815 at 30 and 50 mg/kg did not elicit the phase III-like contractions but produced persistent contractions at the stomach and duodenum in 2 out of 4 conscious animals during the interdigestive state. In the proximal and middle colon, high-amplitude contractions were observed in 5 out of 7 animals by 10-50 mg/kg, p.o. of T-1815. 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.
- 日本平滑筋学会の論文
著者
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ONODA Yuichi
Pharmacological Research Laboratory, Tanabe Seiyaka Co., Ltd.
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YAMADA Kenji
Pharmacological Research Laboratory, Tanabe Seiyaka Co., Ltd.
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