Effects of oral mitemcinal (GM-611), erythromycin, EM-574 and cisapride on gastric emptying in conscious rhesus monkeys.
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 Combined with the results of other studies, these results suggest that mitemcinal may be able to replace the withdrawn drug, cisapride, as the drug of choice for treating delayed gastric emptying.
Yogo
Kenji
K
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Gotemba, Shizuoka 412-8513, Japan.
Onoma
Mitsu
M
Ozaki
Ken-Ichi
K
Koto
Masao
M
Itoh
Zen
Z
Omura
Satoshi
S
Takanashi
Hisanori
H
D000082:Acetaminophen / Q000378:metabolism; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000378:metabolism; D000818:Animals; D020117:Cisapride / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness; D004917:Erythromycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male
D018712:Analgesics, Non-Narcotic; D005765:Gastrointestinal Agents; C090116:Idremcinal; D000082:Acetaminophen; D004917:Erythromycin; C103741:mitemcinal; D020117:Cisapride