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Original Paper

Effects of Mitemcinal (GM-611), an Acid-Resistant Nonpeptide Motilin Receptor Agonist, on the Gastrointestinal Contractile Activity in Conscious Dogs

Ozaki K.a · Yogo K.a · Sudo H.a · Onoma M.a · Kamei K.a · Akima M.a · Koga H.a · Itoh Z.b · Ōmura S.c · Takanashi H.a

Author affiliations

aFuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, bGunma University, Gunma, and cKitasato Institute, Tokyo, Japan

Related Articles for ""

Pharmacology 2007;79:223–235

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: September 11, 2006
Accepted: December 04, 2006
Published online: April 05, 2007
Issue release date: June 2007

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 3

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA

Abstract

The effects of mitemcinal (GM-611) on the gastrointestinal contractile activity were investigated using chronically implanted force transducers in conscious dogs and were compared with the effects of porcine motilin (pMTL), EM-523 and EM-574. In the interdigestive state, intravenous and oral administration of mitemcinal, EM-523 and EM-574 induced the gastrointestinal contractile activity in a manner similar to pMTL. The contractile activity caused by mitemcinal was suppressed by continuous intravenous infusion of a motilin receptor antagonist. In the digestive state, intravenous and oral administration of mitemcinal, EM-523 and EM-574 also stimulated the gastrointestinal contractile activity. Mitemcinal, EM-523 and EM-574 given intravenously increased the gastric contractile activity in a similar dose range; however, mitemcinal was approximately 10 times more potent than EM-523 and EM-574 when administered orally in the digestive state. These results indicate that the mitemcinal-induced gastrointestinal contractile activity operates via motilin receptors and possesses a higher activity than EM-523 and EM-574 when administered orally in conscious dogs in the digestive state. Mitemcinal may therefore be useful in the treatment of several gastrointestinal disorders involving dysmotility, such as gastroparesis and functional dyspepsia, even when administered orally.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: September 11, 2006
Accepted: December 04, 2006
Published online: April 05, 2007
Issue release date: June 2007

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 3

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA


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