Identification of SK-951, a Novel Benzofuran Derivative, as an Agonist to 5-HT4 Receptors.
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- Takeda Motohiro
- Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd.
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- Tsukamoto Katsura
- Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd.
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- Mizutani Yuka
- Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd.
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- Suzuki Tsunemasa
- Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd.
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- Taniyama Kohtaro
- Department of Pharmacology, Nagasaki University School of Medicine
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The pharmacological profile of SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl) ethyl]-5-chloro-2, 3-dihydro-2-methylbenzo[b]furan-7-carboxamide hemifumarate) was identified in relation to serotonin 5-HT3 and 5-HT4 receptors by the receptor binding assay and functional studies. The receptor binding assay showed that SK-951 bound to the 5-HT3 receptor with a high affinity, to the 5-HT4 receptor with relatively higher affinity and to the muscarinic M2 receptor with a low affinity, but not to dopamine D1 and D2 and serotonin 5-HT1 and 5-HT2 and muscarinic M1 and M3 receptors. SK-951 caused relaxations of tunica muscularis mucosae preparations from rat esophagus which were precontracted with carbachol, and the effects were antagonized by GR113808, a selective 5-HT4 antagonist. In the longitudinal muscle with myenteric plexus (LMMP) preparations from guinea pig ileum, SK-951 enhanced the electrically-stimulated contraction of preparations in which the 5-HT1, 5-HT2 and 5-HT3 receptors were blocked, and it enhanced the electrically-stimulated release of [3H]acetylcholine (ACh). These effects of SK-951 were antagonized by GR113808. SK-951 inhibited the 5-HT3 receptor-mediated contractions. These results indicate that SK-951 possesses properties of an agonist for the 5-HT4 receptor and an antagonist for the 5HT3 receptor. Thus, SK-951 is a new and potent 5-HT4-receptor agonist and causes contractions of guinea pig ileum mediated by enhancement of ACh release via the 5-HT4 receptor.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 79 (2), 203-212, 1999
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001204284603392
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- NII論文ID
- 10008682354
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- NII書誌ID
- AA00691188
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- COI
- 1:CAS:528:DyaK1MXhsFyktrs%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 4663513
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- PubMed
- 10202856
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I4663513
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- https://www.jstage.jst.go.jp/article/jjp/79/2/79_2_203/_pdf
- https://search.jamas.or.jp/link/ui/1999158806
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- en
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