Blockade of neuronal tryptamine receptors by metoclopramide

Metoclopramide (0.13, 0.51, 2.0 and 8.1 X 10(-6) M) caused parallel, rightward, shifts in the dose response curves to 5-HT on the isolated rabbit heart. A significant straight line relationship was found between log (5-HT dr--1) and log [metoclopramide] (molar) with a slope of 1.08 +/- 0.13 and giving a pA2 value of 7.20. Metoclopramide did not significantly alter responses to noradrenaline and was 575 times less effective as an inhibitor of DMPP than of 5-HT. The results indicate that metoclopramide is a potent, surmountable and selective antagonist of tryptamine receptors on rabbit cardiac sympathetic nerves.