Awouters: Non-antidopaminergic, non-cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats. Drug Dev. Res. 8:243-250, 1986. 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 mglkg) on the one hand, and direct cholinergic activity (ED50: > 40 mglkg) and peripheral and central antidopamine activity (ED50s: 3.3 and 18.6 mglkg), 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 mglkg for lacrimation and salivation) with their gastrokinetic activity, which was obtained with bethanechol at 0.63 mglkg and with metoclopramide at 1.25 mglkg. 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 mglkg).The present data confirm cisapride as a potent gastrokinetic compound devoid of antidopaminergic or direct cholinergic properties.

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The Monte Carlo method, also called computer simulation, has been applied to the estimation of confidence limits of pharmacological results. An application of this nonparametric method to observations from the passive cutaneous anaphylaxis test in the rat is described. Confidence limits for the sum of five observations are shown to be reproducible with repeated simulation and to be sensitive to changing experimental conditions. A difference between two anti-ovalbumin IgE serum batches has been observed from the empirical distributions produced by the Monte Carlo method.