Comparison of sympathetic modulation induced by single oral doses of mibefradil, amlodipine, and nifedipine in healthy volunteers

Objective: Our objective was to compare the sympathetic modulation induced by oral administration of a single dose of 20 mg of standard nifedipine, of 10 mg of amlodipine, and of 100 mg of mibefradil. Methods: Sixteen healthy male volunteers participated in this double-blind, randomized, placebo-controlled, crossover four-period study. The sympathet ic modulation induced by treatments was evaluated during 24 hours after dru g administration by neurohormonal dosages, hemodynamic parameter measuremen ts, and spectral analysis of heart rate and blood pressure. Results: We observed a significant (P < .05) decrease in diastolic blood pr essure 1 hour after the administration of nifedipine (62 <plus/minus> 9 to 59 +/- 5 mm Hg) with concomitant increases in heart rate (59 +/- 5 to 74 +/ - 8 bpm) and neurohormones (53 +/- 18 to 83 +/- 50 pg/mL for aldosterone, 1 57 +/- 56 to 282 +/- 119 pg/mL for norepinephrine, and 9.8 +/- 5.5 to 40.2 +/- 97.1 pg/mL for active renin). No significant modification of these para meters was observed with amlodipine and mibefradil, except an isolated incr ease of norepinephrine plasma level 2 hours after the administration of mib efradil (133.1 +/- 67.1 to 210.9 +/- 92.5 pg/mL). The spectral analysis ove r 24 hours of Mayer waves of systolic blood pressure did not show any signi ficant change over time in the different groups. When the analysis was perf ormed during the first 4 hours after treatment administration, we observed a decrease of Mayer waves of systolic blood pressure with nifedipine (2.21 +/- 1.45 mm Hg-2 versus 3.53 +/- 1.85 mm Hg-2 with placebo). These results indicate that oral single doses of mibefradil and amlodipine do not induce baroreflex-mediated clinical changes in healthy volunteers. The single oral dose of nifedipine resulted in a marked increase in sympathetic tone and a decrease in systolic blood pressure variability early after oral administr ation. Conclusion: Mibefradil, the nondihydropyridine calcium antagonist, exerts m uch less sympathetic stimulation than nifedipine.