1.
Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and
emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of
emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3.
Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused
emesis in all fasted dogs and in 5 dogs after food.
Atropine (50 mg kg-1 min-1) and
hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce
emesis. 4.
Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of
emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist,
MDL 72222 (1 mg kg-1), reduced
emesis when given alone and combined with
metoclopramide (low dose). The
5-HT4 receptor agonist BRL24924 (
Renzapride, 1 mg kg-1) had no effect on
emesis either alone in combination with
metoclopramide. 6. In conclusion,
erythromycin-induced GI motility disturbances and
emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated,
emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the
dopamine system.