Differential effects of urapidil and doxazosin on heart rate

Eur J Clin Pharmacol. 2007 Mar;63(3):259-62. doi: 10.1007/s00228-006-0256-2. Epub 2007 Jan 16.


Objective: Although alpha-blockers are effective in lowering blood pressure, they may increase heart rate, an unwanted effect that could negatively affect outcome. However, the alpha-blocker urapidil might not increase heart rate due to its additional effect on 5-HT1A receptors. Therefore, we compared the effects of urapidil on heart rate with those of another alpha-blocker, doxazosin.

Methods: We performed a randomised, double-blind, placebo-controlled, cross-over study in 12 healthy males who received single oral doses of 60 mg urapidil, 4 mg doxazosin and placebo. Four hours following drug intake, heart rate and blood pressure were measured at rest and during exercise.

Results: Both doxazosin and urapidil decreased blood pressure to the same extent. Compared to placebo, resting heart rate was significantly increased by doxazosin (+25%, P < 0.05) but not by urapidil (+12%, n.s.). Resting heart rate with doxazosin was significantly higher than with urapidil (P < 0.05). Similarly, the rate pressure product (RPP) at rest was increased by doxazosin (+17%, P < 0.05) but not by urapidil (+6%, n.s.).

Conclusions: We conclude that the increase in heart rate caused by urapidil is less pronounced than that with doxazosin, a property that might favour urapidil in the treatment of arterial hypertension. In addition, only doxazosin (but not urapidil) increased the RPP at rest, a finding that might be helpful to explain why this drug was never shown to improve outcome in the treatment of arterial hypertension.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Adult
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Doxazosin / pharmacology*
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Piperazines / pharmacology*


  • Adrenergic alpha-Antagonists
  • Piperazines
  • urapidil
  • Doxazosin