title: A human trigeminovascular biomarker for antimigraine drugs: A randomised, double-blind, placebo-controlled, crossover trial with sumatriptan.
abstract: Current antimigraine drugs are believed, besides their direct vasoconstrictive effect, to inhibit calcitonin gene-related peptide (CGRP) release from trigeminal nerve endings during migraine. Objective The objective of this report is to establish a biomarker for the CGRP-interfering effect of antimigraine drugs. Methods We quantified the effect of sumatriptan on the trigeminal nerve-mediated rise in forehead dermal blood flow (DBF), induced by capsaicin application (0.6 mg/ml) and electrical stimulation (0.2-1.0 mA), in a randomised, double-blind, placebo-controlled, crossover study in healthy male ( n = 11, age ± SD: 29 ± 8 years) and female ( n = 11, 32 ± 7 years) individuals. Results DBF responses to capsaicin were attenuated by sumatriptan (ΔDBF, mean ± SEM: 82 ± 18 AU, p = 0.0002), but not by placebo (ΔDBF: 21 ± 12 AU, p = 0.1026). Conclusion We demonstrated that sumatriptan inhibits increases in DBF, induced by the release of, most likely, CGRP. Thus, our model may be used as a biomarker to establish the trigeminovascular effects of (potential) antimigraine drugs, such as CGRP receptor antagonists or antibodies directed against CGRP or its receptor.
authors.affiliation: 1 Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Ibrahimi
authors.affiliation: 1 Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, The Netherlands.
authors.forename: Ahj
authors.initials: A
authors.lastname: Danser
authors.affiliation: 2 Department of Neurology, Leiden University Medical Center, The Netherlands.
authors.forename: G M
authors.initials: GM
authors.lastname: Terwindt
authors.affiliation: 1 Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: van den Meiracker
authors.affiliation: 1 Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: MaassenVanDenBrink
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D018170:Sumatriptan / Q000494:pharmacology / Q000627:therapeutic use*; D014276:Trigeminal Nerve / Q000098:blood supply* / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000700:Analgesics; D015415:Biomarkers; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; Migraine; antimigraine therapy; biomarker; sumatriptan; trigeminovascular