Effects of loperamide on acetylcholine and prostaglandin release from isolated guinea pig ileum.

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  • YAGASAKI Osamu
    Department of Veterinary Pharmacology, College of Agriculture, Universitv of Osaka Prefecture
  • SUZUKI Hiroyuki
    Department of Veterinary Pharmacology, College of Agriculture, Universitv of Osaka Prefecture
  • SOHJI Yukinobu
    Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd.

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タイトル別名
  • Effects of loperamide on acetylcholine

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Loperamide, an effective antidiarrheal agent, was investigated in attempts to determine the site of action which underlies the antiperistaltic and other antidiarrheal actions. In in vitro studies, this compound applied in a dose over 10-8 g/ml, inhibited the release of both acetylcholine and prostaglandins during circumferential distension of the intestinal wall, in a dose dependent manner. The inhibited acetylcholine release, but not prostaglandin release, was reversed by naloxone. This suggests that loperamide inhibits acetylcholine release by interacting with opiate receptor sites in the myenteric plexus. The inhibition of prostaglandin release may be due to inhibition of prostaglandin synthesis in the intestine because loperamide prevented the biosynthesis of prostaglandin from arachidonic acid. Although a high concentration of loperamide (10-6 g/ml) inhibited the contraction of the intestine to acetylcholine, this compound inhibited the contraction to nicotine and serotonin at a concentration which had no effect on the contraction to acetylcholine. Thus loperamide apparently inhibits the peristaltic movement principally by reducing the release of acetylcholine and prostaglandin, at least during circumferential distension of the intestinal wall in vitro. The finding that loperamide inhibited the biosynthesis of prostaglandin may lead to elucidation of the mechanism of its antidiarrheal activity.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 28 (6), 873-882, 1978

    公益社団法人 日本薬理学会

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