Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Abstract

Abstract The gastrokinetic activity of cisapride, bethanechol, domperidone, and metoclopramide was tested in rats and compared with the direct cholinergic activity (induction of salivation and lacrimation in rats) and peripheral and central antidopamine activity (antagonism of apomorphine‐induced emesis in dogs and abnormal behaviour in rats, respectively) of the compounds. Cisapride showed a high dissociation between gastrokinetic activity (0.31 mg/kg) on the one hand, and direct cholinergic activity (ED50: ≥ 40 mg/kg) and peripheral and central antidopamine activity (ED50s: 3.3 and 18.6 mg/kg), on the other hand. In contrast, metoclopramide combined antidopamine effects (ED50s: 0.28 and 0.76 mg/kg for peripheral and central activity) and bethanechol direct cholinergic effects (ED50s: 2.7 and 3.6 mg/kg for lacrimation and salivation) with their gastrokinetic activity, which was obtained with bethanechol at 0.63 mg/kg and with metoclopramide at 1.25 mg/kg. Domperidone was found to be a potent and selective antagonist of peripheral dopamine receptors (ED50: 0.0071 mg/kg) but failed to stimulate gastric emptying (ED50: ≥ 10 mg/kg). The present data confirm cisapride as a potent gastrokinetic compound devoid of antidopaminergic or direct cholinergic properties.