The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men

Br J Clin Pharmacol. 2011 May;71(5):708-17. doi: 10.1111/j.1365-2125.2010.03869.x.

Abstract

Aims: To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG).

Methods: Twenty-two healthy male volunteers participated in a randomized, placebo-controlled, double-blind, two-period, crossover study. Subjects received 500 mg telcagepant or placebo followed, 1.5 h later, by 0.4 mg NTG. To assess the haemodynamic response the following vascular parameters were measured: blood pressure, aortic augmentation index (AIx) and brachial artery diameter (BAD). Data are presented as mean (95% confidence interval, CI).

Results: The aortic AIx following NTG decreased by -18.50 (-21.02, -15.98) % after telcagepant vs. -17.28 (-19.80, -14.76) % after placebo. The BAD fold increase following NTG was 1.14 (1.12, 1.17) after telcagepant vs. 1.13 (1.10, 1.15) after placebo. For both AIx and BAD, the hypothesis that telcagepant does not significantly affect the changes induced by NTG is supported (P < 0.0001). In addition, no vasoconstrictor effect of telcagepant could be demonstrated.

Conclusions: Telcagepant did not affect NTG-induced haemodynamic changes. These data suggest that NTG-induced vasodilation is not CGRP dependent.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aorta / drug effects
  • Aorta / physiology
  • Azepines / pharmacology*
  • Blood Pressure / drug effects
  • Brachial Artery / drug effects
  • Brachial Artery / physiology
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions
  • Heart Rate / drug effects
  • Humans
  • Imidazoles / pharmacology*
  • Male
  • Middle Aged
  • Nitroglycerin / pharmacology*
  • Vasodilation / drug effects*
  • Vasodilation / physiology
  • Vasodilator Agents / pharmacology*
  • Young Adult

Substances

  • Azepines
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Imidazoles
  • Vasodilator Agents
  • telcagepant
  • Nitroglycerin