The effect of metoclopramide on QT dynamicity: double-blind, placebo-controlled, cross-over study in healthy male volunteers

Background: Metoclopramide, a central and peripheral dopamine type 2 receptor antagonist, has been used as an attractive and safer alternative to cisapride. However, cardiac side-effects have also been reported with this drug. Aim: To evaluate the effects of intravenous metoclopramide administration on cardiac repolarization using QT dynamicity, a reliable indicator of arrhythmic side-effects. Methods: The effect of metoclopramide on cardiac repolarization was evaluated in 10 healthy male volunteers in the supine position. Metoclopramide (10 mg) or placebo was administered intravenously at random in a double-blind, cross-over manner to the participants during continuous electrocardiographic recording in the supine position. The 30-min stationary segments of the recordings before and after drug administration were used to investigate QT dynamicity. Results: Metoclopramide administration, but not placebo, resulted in steeper QT/RR slopes compared with the pre-drug values (metoclopramide: 0.037 +/- 0.004 vs. 0.064 +/- 0.012; P = 0.041; placebo: 0.045 +/- 0.006 vs. 0.050 +/- 0.004; P = 0.563). In a two-way analysis of variance model, metoclopramide administration also increased the QT variance independently (F = 6.225, P = 0.023). Conclusions: Metoclopramide administration increases the QT/RR slope and QT variance. These findings may partly explain the underlying mechanism of ventricular arrhythmias associated with metoclopramide.