BACKGROUND: The calcitonin gene-related peptide (CGRP) receptor antagonists 
olcegepant and telcagepant are very potent drugs. Both are effective in migraine 
but in doses much higher than would be predicted from receptor binding and other 
in vitro results. This could perhaps suggest an effect of CGRP antagonists 
behind the blood-brain barrier (BBB), i.e. in the central nervous system (CNS).
METHODS: Comparison of doses needed for CGRP blocking effect in vitro with dose 
needed in vivo in man and monkeys. Discussion of these doses in relation to 
doses needed for anti-migraine activity.
RESULTS: In vivo studies in monkeys and man showed that high doses compared to 
doses needed in vitro are needed to block capsaicin-induced in skin blood flow, 
a CGRP-mediated reaction. These doses are close to those needed for 
anti-migraine activity.
CONCLUSION: The apparently high doses of CGRP receptor antagonists, olcegepant 
and telcagepant needed for anti-migraine effect are not so high after all. They 
do not allow a conclusion as to whether CGRP antagonists act on peripheral sites 
or central sites in migraine.