Document Detail

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

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