BIBN4096BS Antagonizes Human α-calcitonin Gene Related Peptide–induced Headache and Extracerebral Artery Dilatation*

Abstract

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 αCGRP (h‐αCGRP)–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‐αCGRP (1.5 Μg/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 (PETCO₂), 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‐αCGRP. 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. Clinical Pharmacology & Therapeutics (2005) 77, 202–213; doi: 10.1016/j.clpt.2004.10.001