PROKINETIC EFFECT OF DOMPERIDONE IN GALLBLADDER - NOT UPON DOPAMINERGIC RECEPTORS

The mechanism of the contractile effect of domperidone on gallbladder smooth muscle has been investigated by using an in-vivo and an in-vitr o model. In the in-vivo part of the study 14 healthy males were admini stered 20 mg domperidone or two placebo tablets orally and gallbladder emptying was measured by ultrasonography. The reduction in the gallbl adder volume was significant compared to the placebo at 45 and 55 min. In the in-vitro part of the study, the gallbladder strips isolated fr om guinea pigs were field stimulated and 10(-6)-10(-4) M concentration s of dopamine were administered before electrical field stimulation (E FS) was repeated. Dopamine exerted no significant effect upon the cont ractions obtained by EFS. The effect of dopamine and domperidone under basal conditions were also explored. Under basal conditions, dopamine neither contracted nor relaxed the gallbladder muscle between 10(-6) and 10(-4) M concentrations when added directly to the organ bath. Bes ides, a significant contraction was observed with 10(-4) M concentrati on of domperidone whereas 10(-7), 10(-6) and 10(-5) M concentrations e xerted no effect. This effect of domperidone was thought to be nonspec ific but inhibited by 10(-6) M atropine, 10(-5) M pirenzepine and abol ished by 10(-6) M tetrodotoxin. In summary, domperidone produces a mod est contraction in human gallbladder. This effect does not seem to occ ur upon dopaminergic receptors in guinea pig models. (C) 1996 The Ital ian Pharmacological Society.