Direct inhibitory effect of erythromycin on human alimentary tract
Aviram Nissan, M.D.
, Herbert R. Freund, M.D.
*, Menachem Hanani, Ph.D.
Department of Surgery and Laboratory of Experimental Surgery, Hadassah University Hospital Mount Scopus and Hebrew University-Hadassah
Medical School, Jerusalem, Israel
Department of Surgery, Hadassah University Hospital Mount Scopus, P.O. Box 24035, Jerusalem, il-91240, Israel
Manuscript received December 17, 2001; revised manuscript January 5, 2002
Background: Erythromycin was found to stimulate motor activity in the upper gastrointestinal tract. However, in several smooth muscle
preparations, it also elicited an inhibitory effect. Our aim was to study the effect of erythromycin in various human alimentary tract smooth
Methods: Using force measurements, we assessed the effect of erythromycin on electrically and chemically evoked contractions of isolated
muscle strips of human gallbladder, small intestine, and colon.
Results: The muscarinic receptor agonist carbachol evoked contraction in gallbladder, ileum, and colonic smooth muscle that were reduded
by erythromycin at 10
Mto72%Ϯ 24%, 77% Ϯ 22%, and 76% Ϯ 22% of control values, respectively. Erythromycin did not affect
contractions evoked by noncholinergic agents. Erythromycin’s inhibitory effects were not altered by nerve blockade, indicating a direct
muscle effect. Eryrthromycin also reduced contractions evoked by electrical stimulation at frequencies of 5, 10, and 20 Hz in the human
gallbladder, ileum, and colon preparations. These contractions were reduced by erythromycin in a reversible and dose-dependent manner.
Conclusions: Erythromycin antagonized direct cholinergic effects on various smooth muscles from the human alimentary tract in a
concentration-dependent manner. © 2002 Excerpta Medica, Inc. All rights reserved.
Keywords: Erythromycin; Smooth muscle; Contractility; Alimentary tract; Gallbladder; Ileum; Colon
The prokinetic activity of erythromycin (EM) is well estab-
lished [1–3]. This activity resembles that of the gastrointes-
tinal hormone motilin, which is released periodically in the
fasting state. In humans and dogs motilin induces phase III
activity and is believed to play a role in the regulation of the
migrating motor complex . Bjornsson and Abrahamsson
 have compared the phase-III-like gastroduodenojejunal
activity induced by EM with the naturally occurring phase
III. They concluded that at low doses, EM is very effective
in inducing phase-III-like activity with a slower propagation
rate. EM was shown to displace motilin from its receptors
, and has been proposed to act as a motilin agonist.
Improvement of gastric emptying in patients with diabetic
gastroparesis who were treated with EM was the ﬁrst clin-
ical application of these properties . Erythromycin has
also been found to exert an inhibitory effect on isolated
longitudinal muscle of guinea-pig small intestine , and on
isolated human bronchial smooth muscle . We have de-
scribed an inhibitory effect of EM on the rat urinary bladder
 and uterus , and on the guinea pig gallbladder .
In these studies EM inhibited smooth muscle contractions
evoked by the muscarinic agonist carbachol, as well as
contractions evoked by electric ﬁeld stimulation. Depoor-
tere and Peeters  characterized this inhibitory effect and
showed that it was mediated through calcium channels.
They concluded, as we did, that these effects were not
mediated by motilin receptors. Furness et al  also
showed that EM inhibited contractile responses of the guin-
ea-pig ileum induced by electrical stimulation and carba-
The possible prokinetic action of EM on the colon is of
particular interest as it may have clinical application for the
treatment of constipation. In an in vitro study no effect of
motilin was observed on human circular colonic muscle
 while Van Assche et al  showed that EM and
motilin contracted isolated segments of human colon by
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The American Journal of Surgery 183 (2002) 413–418
0002-9610/02/$ – see front matter © 2002 Excerpta Medica, Inc. All rights reserved.