Effects of cholinoceptor and 5‐hydroxytryptamine3 receptor antagonism on erythromycin‐induced canine intestinal motility disruption and emesis

• Published in: British journal of pharmacology Vol. 108; no. 1; pp. 44 - 49
• Main Authors: Qin, Xin Yu, Pilot, Marie‐Anne, Thompson, Hilary, Scott, Mark
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.1993; Nature Publishing
• Subjects: 5‐hydroxytryptamine; Animals; atropine; Atropine - pharmacology; Benzamides - pharmacology; Biological and medical sciences; Bridged Bicyclo Compounds - pharmacology; Bridged Bicyclo Compounds, Heterocyclic; cholinergic; Cholinergic Antagonists; Dogs; Drug toxicity and drugs side effects treatment; Electromyography; emesis; Erythromycin; Erythromycin - administration & dosage; Erythromycin - pharmacology; Female; gastrointestinal motility; Gastrointestinal Motility - drug effects; Hexamethonium; Hexamethonium Compounds - pharmacology; Injections, Intravenous; Intestine, Small - drug effects; Intestine, Small - metabolism; Male; MDL72222; Medical sciences; metoclopramide; Metoclopramide - pharmacology; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Pharmacology. Drug treatments; Renzapride; Serotonin Antagonists - pharmacology; Toxicity: digestive system; Tropanes - pharmacology; Vomiting - chemically induced; Fissipedia; Carnivora; Motility; Toxicity; Gut; Erythromycin; Macrolide; Motility disorder; Vertebrata; Antibiotic; Cholinergic receptor; Mammalia; Vomiting; Animal; S3 receptor; Digestive diseases; Intestinal disease; Dog
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13437.x

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 μg 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.