Falipamil (AQ-A 39) is a new verapamil derivative which exerts antitachycardic effects by a direct action on the sinus node. Its effects on heart rate (HR), blood pressure (BP) and ECG intervals were studied in 12 healthy volunteers, at rest and during bicycle exercise tests. In a double-blind, cross-over, single-dose study, the effects of falipamil (100 and 200 mg) during 8-h post-dosing were compared with those of placebo. Falipamil did not modify resting HR, BP, and electrocardiogram (ECG) intervals significantly. Maximal exercise HR significantly decreased by 5.3 +/- 2.9 (SD)% and 11.2 +/- 3.6% 2 h after the 100- and 200-mg dose respectively, whereas placebo had no effect. Exercise BP was not significantly modified by falipamil. The slopes of HR-workload relationships significantly decreased with falipamil. Peak plasma concentrations of falipamil occurred 1-1.5 h after absorption, and the falipamil-induced decrease in exercise HR over 8 h postdosing was proportional to falipamil plasma concentrations. These results suggest that falipamil decreases HR at exercise in normal subjects and may exert antianginal effects in patients with myocardial ischemia.