Mechanism of gastroprokinetic effect of EM523, an erythromycin derivative, in dogs.
BACKGROUND
The pharmacological properties of EM523, a nonpeptide motilin agonist, have not been well characterized.


METHODS
The prokinetic effect of EM523 on motor-stimulating activity in the stomach, duodenum, and jejunum in seventeen conscious dogs was studied using force transducers implanted long term. EM523 (0.3-10.0 micrograms/kg) and receptor antagonists were injected intravenously during the interdigestive state.


RESULTS
EM523 induced phase III-like contractions in a dose-dependent manner, and the contractions were inhibited dose dependently by pretreatment with cholinergic and 5-HT3 receptor antagonists and dopamine but not by adrenoceptor and opiate antagonists or methysergide. The plasma immunoreactive motilin level was increased after EM523 to 60% of the mean maximum value during the spontaneous phase III contractions. Pretreatment with anti-canine motilin serum inhibited EM523-induced contractions by 19.2% in the motor index, but the contractile pattern was not affected.


CONCLUSIONS
EM-523-induced phase III-like contractions are brought about through the cholinergic neural pathway and 5-HT3 receptors, and endogenous motilin release is partially involved.
Ohtawa
M
M
Gastrointestinal Laboratories, Gunma University, Maebashi, Japan.
Mizumoto
A
A
Hayashi
N
N
Yanagida
K
K
Itoh
Z
Z
Omura
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007106:Immune Sera / Q000276:immunology; D008297:Male; D009037:Motilin / Q000097:blood / Q000276:immunology
D007106:Immune Sera; D009037:Motilin; D004917:Erythromycin; D001285:Atropine; C061752:EM 523