BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced headache and extracerebral artery dilatation

Clin Pharmacol Ther. 2005 Mar;77(3):202-13. doi: 10.1016/j.clpt.2004.10.001.


Background and objective: Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine pathogenesis. BIBN4096BS is the first CGRP receptor antagonist available for human studies, and its efficacy in the acute treatment of migraine has been demonstrated. We investigated the ability of BIBN4096BS to inhibit human alphaCGRP (h-alphaCGRP)-induced headache and cerebral hemodynamic changes in healthy volunteers.

Methods: Ten healthy volunteers completed this double-blind, placebo-controlled crossover study with 2.5 mg BIBN4096BS and placebo as pretreatments before a 20-minute intravenous infusion of h-alphaCGRP (1.5 microg/min). Transcranial Doppler ultrasonography was used to measure blood flow velocity in the middle cerebral artery (MCA); regional and global cerebral blood flow (CBF) was measured by xenon 133 inhalation single-photon emission computed tomography. The temporal and radial artery diameter was measured by high-frequency ultrasound. Systemic hemodynamics, end-tidal partial pressure of carbon dioxide (PETCO(2)), and headache were monitored.

Results: Of the 10 volunteers, 6 had a CGRP-induced headache during the in-hospital phase after placebo pretreatment but none after BIBN4096BS (P = .031). BIBN4096BS did not affect changes in the diameter of the MCA or changes in CBF induced by h-alphaCGRP. Vasodilatation of the extracranial arteries was, however, significantly inhibited (P < .001 for temporal artery and P = .001 for radial artery).

Conclusions: These results show that BIBN4096BS effectively prevents CGRP-induced headache and extracerebral vasodilatation but does not significantly affect the induced cerebral hemodynamic changes.

Publication types

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

MeSH terms

  • Adult
  • Calcitonin Gene-Related Peptide / analogs & derivatives
  • Calcitonin Gene-Related Peptide / blood
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / physiology*
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Cross-Over Studies
  • Female
  • Headache / chemically induced
  • Headache / prevention & control*
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Injections, Intravenous
  • Male
  • Piperazines / adverse effects
  • Piperazines / blood
  • Piperazines / pharmacokinetics*
  • Quinazolines / adverse effects
  • Quinazolines / blood
  • Quinazolines / pharmacokinetics*
  • Receptors, Calcitonin Gene-Related Peptide / administration & dosage
  • Receptors, Calcitonin Gene-Related Peptide / therapeutic use
  • Reference Values
  • Tomography Scanners, X-Ray Computed
  • Ultrasonography, Doppler, Transcranial / methods
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • BIBN 4096BS
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Piperazines
  • Quinazolines
  • Receptors, Calcitonin Gene-Related Peptide
  • Calcitonin Gene-Related Peptide