新規ヒスタミンH<SUB>2</SUB>受容体拮抗薬, キュバン誘導体(SWR-104SA)の酸分泌及び実験的潰瘍形成に対する作用

• 新川 蘭順

• 木曽 達也

• 片岡 博文

• 礒井 孝

• 柿田 孝雄

• 正垣 武志

• 大坪 義和

書誌事項

タイトル別名

• Effects of Cuban Analog (SWR-104SA), a New Histamine H<SUB>2</SUB> Receptor Antagonist, on Gastric Acid Secretion and Experimental Ulcer Formation
• 新規ヒスタミンH2受容体拮抗薬,キュバン誘導体(SWR-104SA)の酸分泌及び実験的潰瘍形成に対する作用
• シンキ ヒスタミン H2 ジュヨウタイ キッコウヤク キュバン ユウドウタイ

抄録

The antagonism of histamine H₂-receptor by SWR-104SA (1'-bromo-N-[3-[3-(1-piperidinylmethyl) phenoxy] propyl]-spiro [1, 3-dioxolane-2, 9'-pentacyclo-[4. 3. 0. 0.^{2, 5}0.^{3, 8}0.^{4, 7}] nonane]-4'-carboxamide monooxalate) was estimated using the isolated guinea-pig atrium and gastric acid secretion in rats. The concentration-response curves for the positive chronotropic effect of histamine on the atrium were displaced to the right in parallel without change in the maximum response by SWR-104SA and roxatidine acetate hydrochloride (roxatidine). The pA₂ values of SWA-104SA and roxatidine acetate hydrochloride were 7.27 and 7.38, respectively. The slopes of the regression line of log (DR-1) against log SWR-104SA and roxatidine concentration were 1.00 and 0.92, respectively. There was no significant difference between the two compounds with respect to the histamine H₂-receptor antagonism and/or binding manner in vitro. In the rat gastric fistula model stimulated by histamine, however, antisecretory potency of SWR-104SA was 3 times less than that of roxatidine. SWR-104SA given p.o. prevented the formation of gastric lesion induced by HCl-ethanol and indomethacin dose-dependently, roxatidine also prevented its formation by HCl-ethanol, but failed to prevent that by indomethacine. These antiulcer activities of SWR-104SA were shown at the lesser doses of antisecretory activity. On the other hand, roxatidine did not prevent the ulcer formation at the same dose level of antisecretory activity. These results indicate that the antiulcer effect of SWR-104SA is not caused by the antisecretory action alone. In addition, the mucosal protective activity of SWR-104SA for HCl-ethanol induced gastric lesion was independent of endogenous prostaglandins. Moreover SWR-104SA had inhibitory effects on indomethacin-induced gastric hypermotility in rats. These actions may partly explain the gastric protection of this compound and additional mechanisms such as mucosal blood flow could be involved in the antiulcer efficacy. Consequently, it appears that SWR-104SA is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

収録刊行物

• 薬学雑誌

  薬学雑誌 116 (10), 783-791, 1996

  公益社団法人 日本薬学会

キーワード

• antiulcer activity
• gastric acid antisecretory activity
• histamine H<SUB>2</SUB>-receptor antagonist
• 1'-bromo-N-[3-[3-(1-piperidinylmethyl) phenoxy]-propyl]-spiro [1, 3-dioxolane-2, 9'-pentacyclo [4. 3. 0. 0.<SUP>2, 5</SUP>0.<SUP>3, 8</SUP>0.<SUP>4, 7</SUP>] nonane]-4'-carboxamide monooxalate

詳細情報

• CRID: 1390282681131784576
• NII論文ID: 110003648999
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi1947.116.10_783
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 4058547
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4058547
• Web Site: https://www.jstage.jst.go.jp/article/yakushi1947/116/10/116_10_783/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1997065527
• データソース種別:
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  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可