Effect of a new colonic prokinetic compound, T-1815, on gastrointestinal motility in anesthetized and conscious fasted dogs.
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.
Yamada
K
K
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama.
Onoda
Y
Y
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D003243:Consciousness; D004285:Dogs; D005215:Fasting; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D011437:Propylamines / Q000008:administration & dosage / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*
D001626:Bethanechol Compounds; D011437:Propylamines; D013876:Thiophenes; D018723:Bethanechol; C081988:T 1815