DOSE-DEPENDENT HEART-RATE REDUCING EFFECT OF NIZATIDINE, A HISTAMINE-H2-RECEPTOR ANTAGONIST

1 Twelve healthy subjects were treated in a randomised placebo-control led crossover study with placebo, 150 mg, 300 mg, and 600 mg nizatidin e, 100 mg pirenzepine, and 300 mg nizatidine plus 100 mg pirenzepine f or 1 week each. 2 On the seventh treatment day, heart rate, blood pres sure, systolic time intervals, impedance cardiographic and Doppler ult rasound variables were measured. 3 Stroke volume and blood pressure we re not altered by nizatidine and/or pirenzepine. By contrast, heart ra te and cardiac output significantly (P < 0.05) decreased in a dose-dep endent manner 1.5 and 3 h after administration of 300 and 600 mg nizat idine. Treatment with 150 mg nizatidine led to similar though non-sign ificant trends. 4 While a slightly insignificant rise in heart rate wa s detected with pirenzepine alone, heart rate and cardiac output remai ned unchanged upon combined nizatidine and pirenzepine treatment as co mpared with placebo and baseline values. 5 In conclusion, nizatidine r educed heart rate and cardiac output in a dose-dependent manner, where as this negative chronotropic effect was counteracted by concurrent ad ministration of the anti-cholinergic drug pirenzepine.