CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine

There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN. Methods: In a double-blind-cross-over study, 13 migraine without aura (MO) patients were administered GTN 0.5 mu g/kg/minute for 20 minutes and subsequently BIBN4096BS (olcegepant) 10 mg or placebo. Headache scores and development of MO were followed for 24 hours. Results: MO developed in seven of 13 with olcegepant and in nine of 13 with placebo (p = 0.68). The headache scores were similar after the two treatments (p = 0.58). Thus CGRP receptor blockade did not prevent GTN-induced migraine. Conclusions: The present study indicates that NO does not induce migraine by liberating CGRP. The most likely explanation for our findings is that CGRP has its effect higher than NO in the cascade of events leading to MO attacks.