Reduction of Wrap Restraint Stress-Induced Defecation by MKC-242, a Novel Benzodioxan Derivative, via 5-HT1A-Receptor Agonist Action in Rats.

• Abe Michikazu

  Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation

• Saito Ken-Ichi

  Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation

書誌事項

タイトル別名

• Reduction of Wrap Restraint Stress-Indu

抄録

Effects of MKC-242 (5-｛3-[((2S)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy｝-1, 3-benzodioxole HCl), a novel 5-HT_1A-receptor agonist, and reference compounds on wrap restraint stress-induced defecation were evaluated in rats. Wrapping restraint stress increased defecation in rats. The increase was attenuated by putative 5-HT_1A-receptor agonists, MKC-242 and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The suppressive effect of MKC-242 on wrap stress-induced defecation was antagonized by prior administration of a 5-HT_1A-receptor antagonist, WAY100135. MKC-242 did not affect spontaneous defecation and 5-HT-induced defecation. Diazepam and amitriptyline also significantly reduced the stress-induced defecation. However, amitriptyline showed a potent anti-cholinergic effect in the oxotremorine-induced tremor test and reduced spontaneous defecation. In contrast to MKC-242 and 8-OH-DPAT, buspirone and tandospirone tended to suppress the increase at high doses. A major metabolite of buspirone and tandospirone, 1-(2-pyrimidinyl)piperazine, antagonized the suppressive effect of MKC-242. These findings suggest that stimulation of 5-HT_1A receptors reduces stress-induced defecation but not spontaneous and 5-HT-induced defecation and that MKC-242 may be useful for the treatment of irritable bowel syndrome.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 77 (3), 211-217, 1998

  公益社団法人 日本薬理学会

キーワード

• MKC-242
• 5-HT<SUB>1A</SUB> receptor
• Stress
• Irritable bowel syndrome
• Defecation

詳細情報

• CRID: 1390282679261984640
• NII論文ID: 10008193202
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.77.211
• COI: 1:CAS:528:DyaK1cXkvVOlsL4%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 4525737
• PubMed: 9717768
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4525737
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819311059?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819311059?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/77/3/77_3_211/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1999018905
• 本文言語コード: en
• データソース種別:
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  • NDL
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