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.
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.
Authors: Chi-Chung Li; Steve Vermeersch; William S Denney; William P Kennedy; John Palcza; Adrianna Gipson; Tae H Han; Rebecca Blanchard; Inge De Lepeleire; Marleen Depré; M Gail Murphy; Kristien Van Dyck; Jan N de Hoon Journal: Br J Clin Pharmacol Date: 2015-05 Impact factor: 4.335
Authors: Candler Paige; Isabel Plasencia-Fernandez; Moeno Kume; Melina Papalampropoulou-Tsiridou; Louis-Etienne Lorenzo; Eric T David; Lucy He; Galo L Mejia; Christopher Driskill; Francesco Ferrini; Andrew L Feldhaus; Leon F Garcia-Martinez; Armen N Akopian; Yves De Koninck; Gregory Dussor; Theodore J Price Journal: J Neurosci Date: 2022-01-20 Impact factor: 6.709
Authors: Christopher S Walker; Sajedeh Eftekhari; Rebekah L Bower; Andrea Wilderman; Paul A Insel; Lars Edvinsson; Henry J Waldvogel; Muhammad A Jamaluddin; Andrew F Russo; Debbie L Hay Journal: Ann Clin Transl Neurol Date: 2015-04-01 Impact factor: 4.511