Possible site of action of CGRP antagonists in migraine

TY - JOUR

T1 - Possible site of action of CGRP antagonists in migraine

AU - Tfelt-Hansen, Peer

AU - Olesen, Jes

PY - 2011/4

Y1 - 2011/4

N2 - 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 invitro 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 invitro with dose needed invivo in man and monkeys. Discussion of these doses in relation to doses needed for anti-migraine activity. Results: Invivo studies in monkeys and man showed that high doses compared to doses needed invitro 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.

AB - 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 invitro 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 invitro with dose needed invivo in man and monkeys. Discussion of these doses in relation to doses needed for anti-migraine activity. Results: Invivo studies in monkeys and man showed that high doses compared to doses needed invitro 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.

U2 - 10.1177/0333102411398403

DO - 10.1177/0333102411398403

M3 - Review

SN - 0333-1024

VL - 31

SP - 748

EP - 750

JO - Cephalalgia

JF - Cephalalgia

IS - 6

ER -