title: Effects of mitemcinal (GM-611), an acid-resistant nonpeptide motilin receptor agonist, on the gastrointestinal contractile activity in conscious dogs.
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.
authors.affiliation: Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Yogo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sudo
authors.forename: Mitsu
authors.initials: M
authors.lastname: Onoma
authors.forename: Kenshi
authors.initials: K
authors.lastname: Kamei
authors.forename: Michitaka
authors.initials: M
authors.lastname: Akima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.forename: Zen
authors.initials: Z
authors.lastname: Itoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
authors.forename: Hisanori
authors.initials: H
authors.lastname: Takanashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004063:Digestion; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D009037:Motilin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000037:antagonists & inhibitors
chemical_list: D005765:Gastrointestinal Agents; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; C090116:Idremcinal; D009037:Motilin; D004917:Erythromycin; C103741:mitemcinal; C061752:EM 523