BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced headache and extracerebral artery dilatation.
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.
Petersen
Kenneth A
KA
Danish Headache Center, University of Copenhagen and Department of Neurology, Glostrup University Hospital, KAS Glostrup, DK-2600 Glostrup, Denmark. kapetersen@dadlnet.dk
Lassen
Lisbeth H
LH
Birk
Steffen
S
Lesko
Lynna
L
Olesen
Jes
J
D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000627:therapeutic use; D012016:Reference Values; D015898:Tomography Scanners, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant