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Effects of Oral Mitemcinal (GM-611), Erythromycin, EM-574 and Cisapride on Gastric Emptying in Conscious Rhesus Monkeys

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Abstract

We assessed and compared the effects of oral mitemcinal (an orally active, erythromycin-derived motilin-receptor agonist; Code name: GM-611), erythromycin, EM-574 and cisapride on gastric emptying in conscious Rhesus monkeys using the acetaminophen method. Mitemcinal and erythromycin induced significant, dose-dependent increases in indices of gastric emptying, but mitemcinal required a much lower dose for the same effect. Cisapride induced a bell-shaped dose response, and EM-574, a potent erythromycin derivative and originally developed as an enteric coated formulation, had little effect when it was given orally uncoated. Since our previous study showed that response to motilin is similar in Rhesus monkeys and humans, these results suggest that oral mitemcinal may be effective for the treatment of symptoms in human disorders related to delayed gastric emptying (e.g., functional dyspepsia and gastroparesis). Combined with the results of other studies, these results suggest that mitemcinal may be able to replace the withdrawn drug, cisapride, as the drug of choice for treating delayed gastric emptying.

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Acknowledgments

The authors wish to thank Mr. Geoffrey Read for his excellent editorial assistance and Ms. Junko Arakaki for her secretarial assistance. The authors also wish to thank Mr. Toyokazu Matsu-ura, Mr. Hajime Sano, Ms. Akiko Hiura, Ms. Mayumi Miyaguchi and Ms. Yuriko Seto-Ozaki for their excellent technical collaboration in the animal experiments.

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Authors and Affiliations

  1. Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Gotemba, Shizuoka, 412-8513, Japan

    Kenji Yogo, Mitsu Onoma, Ken-ichi Ozaki & Hisanori Takanashi

  2. Chugai Research Institute for Medical Science, Inc, Gotemba, Shizuoka, 412-8513, Japan

    Masao Koto

  3. Gunma University, Maebashi, Gunma, 371-8512, Japan

    Zen Itoh

  4. The Kitasato Institute, Minato-ku, Tokyo, 108-8642, Japan

    Satoshi Ōmura

  5. Project Management Department, Chugai Pharmaceutical Co., Ltd, 1–1 Nihonbashi-Muromachi 2-Chome, Chuo-ku, Tokyo, 102-8324, Japan

    Hisanori Takanashi

Authors
  1. Kenji Yogo
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  2. Mitsu Onoma
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  3. Ken-ichi Ozaki
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  4. Masao Koto
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  5. Zen Itoh
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  6. Satoshi Ōmura
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  7. Hisanori Takanashi
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Correspondence to Hisanori Takanashi.

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Yogo, K., Onoma, M., Ozaki, Ki. et al. Effects of Oral Mitemcinal (GM-611), Erythromycin, EM-574 and Cisapride on Gastric Emptying in Conscious Rhesus Monkeys. Dig Dis Sci 53, 912–918 (2008). https://doi.org/10.1007/s10620-007-9951-9

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  • DOI: https://doi.org/10.1007/s10620-007-9951-9

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