| Identification of SK-951, a novel benzofuran derivative, as an agonist to 5-HT4 receptors. | |
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MedLine Citation:
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PMID: 10202856 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 5-HT3 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. |
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Authors:
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M Takeda; K Tsukamoto; Y Mizutani; T Suzuki; K Taniyama |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Japanese journal of pharmacology Volume: 79 ISSN: 0021-5198 ISO Abbreviation: Jpn. J. Pharmacol. Publication Date: 1999 Feb |
Date Detail:
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Created Date: 1999-06-29 Completed Date: 1999-06-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2983305R Medline TA: Jpn J Pharmacol Country: JAPAN |
Other Details:
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Languages: eng Pagination: 203-12 Citation Subset: IM |
Affiliation:
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Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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metabolism* Animals Benzofurans / pharmacology* Bicyclo Compounds, Heterocyclic / pharmacology* Carbachol / pharmacology Cisapride / pharmacology Electric Stimulation Esophagus / drug effects Guinea Pigs Ileum / drug effects Indoles / pharmacology Male Muscle Contraction / drug effects* Muscle Relaxation / drug effects* Muscle, Smooth / drug effects* Protein Binding Rats Rats, Sprague-Dawley Receptors, Dopamine / metabolism Receptors, Muscarinic / metabolism Serotonin Agonists / pharmacology* Sulfonamides / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Benzofurans; 0/Bicyclo Compounds, Heterocyclic; 0/Indoles; 0/Receptors, Dopamine; 0/Receptors, Muscarinic; 0/SK 951; 0/Serotonin Agonists; 0/Sulfonamides; 144625-51-4/GR 113808; 51-83-2/Carbachol; 51-84-3/Acetylcholine; 81098-60-4/Cisapride |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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