An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs.
The effect of an erythromycin derivative, EM-523, on gastrointestinal motility was investigated in conscious dogs and compared with that of motilin cisapride, trimebutine and metoclopramide. In the fasting state, EM-523 given i.v. or i.d. at 3 micrograms/kg or more induced contractions in the stomach that migrated along the small intestine. The pattern of the contractions was very similar to that induced by motilin. In the digestive state, EM-523 increased the amplitude of gastric contractions. Cisapride and metoclopramide increased gastrointestinal motility both in the fasting and digestive states; however, their contractile pattern was different from that of EM-523. Trimebutine did not induce gastric motility in the fasting state but rather decreased gastric motility in the digestive state. The contractions induced by EM-523 and motilin were inhibited by atropine but were not affected by naloxone, suggesting that the cholinergic pathway is important in the exertion of their action. These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth.
Inatomi
N
N
Biology Research Laboratories, Takeda Chemical Industries, Osaka, Japan.
Satoh
H
H
Maki
Y
Y
Hashimoto
N
N
Itoh
Z
Z
Omura
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005215:Fasting; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D009037:Motilin / Q000494:pharmacology*; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; D014839:Vomiting / Q000139:chemically induced
D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin; D004917:Erythromycin; D001285:Atropine; C061752:EM 523