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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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 sympathetic modulation induced by treatments was evaluated during 24 hours after drug administration by neurohormonal dosages, hemodynamic parameter measurements, and spectral analysis of heart rate and blood pressure. RESULTS: We observed a significant (P <.05) decrease in diastolic blood pressure 1 hour after the administration of nifedipine (62 +/- 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, 157 +/- 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 parameters was observed with amlodipine and mibefradil, except an isolated increase of norepinephrine plasma level 2 hours after the administration of mibefradil (133.1 +/- 67.1 to 210.9 +/- 92.5 pg/mL). The spectral analysis over 24 hours of Mayer waves of systolic blood pressure did not show any significant change over time in the different groups. When the analysis was performed 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 administration. CONCLUSION: Mibefradil, the nondihydropyridine calcium antagonist, exerts much less sympathetic stimulation than nifedipine.[1]

References

  1. Comparison of sympathetic modulation induced by single oral doses of mibefradil, amlodipine, and nifedipine in healthy volunteers. Ragueneau, I., Sao, A.B., Démolis, J.L., Darné, B., Funck-Brentano, C., Jaillon, P. Clin. Pharmacol. Ther. (2001) [Pubmed]
 
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