N. Inatomi et al., VAGUS-DEPENDENT AND VAGUS-INDEPENDENT MECHANISMS OF ACTION OF THE ERYTHROMYCIN DERIVATIVE EM574 AND MOTILIN IN DOGS, Japanese Journal of Pharmacology, 71(1), 1996, pp. 29-38
The motor-stimulating action of de(N-methyl)-N-isopropyl-8,9-anhydroer
ythromycin A 6,9-hemiacetal (EM574) on the upper gastrointestinal trac
t was studied in fasted conscious dogs using chronically implanted for
ce transducers and compared with those of porcine motilin and cisaprid
e. EM574 induced gastric phase III-like migrating contractions and inc
reased the plasma motilin levels slightly. The gastric motility induce
d by low doses of EM574 and motilin was abolished by a 5HT(3)-receptor
antagonist ondansetron and acute vagal blockade, whereas under these
conditions, high doses of both agents induced contractions, which were
abolished by atropine. Cisapride-induced gastric motility was inhibit
ed by atropine and acute vagal blockade, but not by ondansetron. EM574
did not stimulate gastric secretion in the basal state. These results
indicate that EM574- and motilin-induced gastrointestinal motility is
attributable mainly to motor-stimulating vagal cholinergic neurons, a
nd 5HT(3)-receptors are probably involved in the process. At high dose
s, EM574 and motilin also appear to stimulate cholinergic neurons in a
non-vagal pathway, probably the enteric nervous system.