Effects of KW-5617 (Zaldaride Maleate), a Potent and Selective Calmodulin Inhibitor, on Secretory Diarrhea and on Gastrointestinal Propulsion in Rats.

• Aikawa Nobuo

  Department of Pharmacology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.

• Karasawa Akira

  Department of Pharmacology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.

書誌事項

タイトル別名

• Effects of KW-5617 Zaldaride Maleate a

抄録

KW-5617 (zaldaride maleate), 1, 3-dihydro-1-[1-[(4-methyl-4H, 6H-pyrrolo[1, 2-α][4, 1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one maleate, is a selective calmodulin inhibitor. We studied the effects of KW-5617 on secretory diarrhea and gastrointestinal propulsion in rats, as compared with those of loperamide, a conventional anti-diarrheal drug. Diarrhea was induced in rats either by 16, 16-dimethyl prostaglandin E₂ (500 μg/kg, i.p.) or by castor oil (1 ml/100 g body weight, p.o.). In the 16, 16-dimethyl prostaglandin E₂ model, KW-5617 at the doses of 3 mg/kg (p.o.) and higher ameliorated the diarrhea. Similarly, loperamide improved the diarrhea, the activity of loperamide being equivalent to that of KW-5617. In the castor oil model, KW-5617 significantly delayed the onset of diarrhea at the doses of 3 mg/kg (p.o.) and higher, while loperamide delayed the onset of diarrhea at the doses of 0.3 mg/kg (p.o.) and higher. KW-5617 only at the high doses of 30 and 100 mg/kg (p.o.) reduced gastric emptying, small intestinal propulsion, proximal colonic propulsion and distal colonic propulsion. In contrast, loperamide at its anti-diarrheal doses inhibited gastrointestinal propulsion. Our results show that KW-5617, unlike loperamide, at its anti-diarrheal doses does not exert anti-propulsive effects in rats. KW-5617 may be a useful drug for the treatment of diarrhea in terms of less side effects such as constipation.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 76 (2), 199-206, 1998

  公益社団法人 日本薬理学会

キーワード

• KW-5617
• Loperamide
• Diarrhea
• Zaldaride
• Gastrointestinal propulsion

詳細情報

• CRID: 1390001204286043520
• NII論文ID: 10008191597
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.76.199
• COI: 1:CAS:528:DyaK1cXht12ntrc%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 4416246
• PubMed: 9541283
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4416246
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819312296?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819312296?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/76/2/76_2_199/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1998201996
• 本文言語コード: en
• データソース種別:
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