OBJECTIVES: Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. BACKGROUND: Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. METHODS: In a single-blind placebo-controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine. RESULTS: Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). CONCLUSIONS: In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction.