Reduction of Wrap Restraint Stress-Induced Defecation by MKC-242, a Novel Benzodioxan Derivative, via 5-HT1A-Receptor Agonist Action in Rats.
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- Abe Michikazu
- Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation
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- Saito Ken-Ichi
- Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation
Bibliographic Information
- Other Title
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- Reduction of Wrap Restraint Stress-Indu
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Abstract
Effects of MKC-242 (5-{3-[((2S)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy}-1, 3-benzodioxole HCl), a novel 5-HT1A-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-HT1A-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-HT1A-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-HT1A 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.
Journal
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 77 (3), 211-217, 1998
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282679261984640
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- NII Article ID
- 10008193202
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DyaK1cXkvVOlsL4%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 4525737
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- PubMed
- 9717768
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I4525737
- https://api.elsevier.com/content/article/PII:S0021519819311059?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819311059?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/77/3/77_3_211/_pdf
- https://search.jamas.or.jp/link/ui/1999018905
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed