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Effects of cholinoceptor and 5‐hydroxytryptamine 3 receptor antagonism on erythromycin‐induced canine intestinal motility disruption and emesis
Author(s) -
Qin Xin Yu,
Pilot MarieAnne,
Thompson Hilary,
Scott Mark
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13437.x
Subject(s) - metoclopramide , motility , hexamethonium , atropine , erythromycin , receptor antagonist , agonist , medicine , antagonist , endocrinology , biology , pharmacology , methysergide , receptor , vomiting , antibiotics , biochemistry , genetics
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‐hydroxytryptamine 3 (5‐HT 3 ) receptor antagonist, MDL 72222 (1 mg kg −1 ), reduced emesis when given alone and combined with metoclopramide (low dose). The 5‐HT 4 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.