2,951
Views
93
CrossRef citations to date
0
Altmetric
Review

Gepants for the treatment of migraine

ORCID Icon & ORCID Icon
Pages 555-567 | Received 28 Jun 2018, Accepted 10 May 2019, Published online: 17 May 2019

References

  • Ferrari MD, Goadsby PJ, Roon KI, et al. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia. 2002;22:633–658.
  • Geraud G, Keywood C, Senard JM. Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans. Headache. 2003;43:376–388.
  • Negro A, Martelletti P. Chronic migraine plus medication overuse headache: two entities or not? J Headache Pain. 2011;12:593–601.
  • Thorlund K, Toor K, Wu P, et al. Comparative tolerability of treatments for acute migraine: A network meta-analysis. Cephalalgia. 2017;37:965–978.
  • Dodick D, Lipton RB, Martin V, et al. Consensus statement: cardiovascular safety profile of triptans (5- HT1B/1D agonists) in the acute treatment of migraine. Headache. 2004;44:414–425.
  • Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28:183–187.
  • Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol. 2013;75:365–391.
  • Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97:553–622.
  • May A. Understanding migraine as a cycling brain syndrome: reviewing the evidence from functional imaging. Neurol Sci. 2017;38:125–130.
  • Liu Y, Broman J, Zhang M, et al. Brainstem and thalamic projections from a craniovascular sensory nervous centre in the rostral cervical spinal dorsal horn of rats. Cephalalgia. 2009;29:935–948.
  • Malick A, Burstein R. Cells of origin of the trigeminohypothalamic tract in the rat. J Comp Neurol. 1998;400:125–144.
  • Malick A, Strassman RM, Burstein R. Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J Neurophysiol. 2000;84:2078–2112.
  • Williams MN, Zahm DS, Jacquin MF. Differential foci and synaptic organization of the principal and spinal trigeminal projections to the thalamus in the rat. Eur J Neurosci. 1994;6:429–453.
  • Noseda R, Jakubowski M, Kainz V, et al. Cortical projections of functionally identified thalamic trigeminovascular neurons: implications for migraine headache and its associated symptoms. J Neurosci. 2011;31:14204–14217.
  • Edvinsson L, Uddman R. Neurobiology in primary headaches. Brain Res Brain Res Rev. 2005;48:438–456.
  • Eftekhari S, Salvatore CA, Calamari A, et al. Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion. Neuroscience. 2010;169:683–696.
  • McCulloch J, Uddman R, Kingman TA, et al. Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci U S A.1986 Aug;83(15):5731-5735.
  • Wolff HG. Headache mechanisms. McGill Med J. 1946;15:127–169.
  • Amin FM, Asghar MS, Hougaard A, et al. Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol. 2013;12:454–461.
  • Wienecke T, Olesen J, Ashina M. Discrepancy between strong cephalic arterial dilatation and mild headache caused by prostaglandin D2 (PGD2). Cephalalgia. 2011;31:65–76.
  • Gallai V, Sarchielli P, Floridi A, et al. Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia. 1995;15:384–390.
  • Cernuda-Morollón E, Larrosa D, Ramón C, et al. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013;81:1191–1196.
  • Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol. 1993;33:48–56.
  • Juhasz G, Zsombok T, Jakab B, et al. Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia. 2005;25:179–183.
  • Lassen LH, Jacobsen VB, Haderslev PA, et al. Involvement of calcitonin gener-elated peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain. 2008;9:151–157.
  • Hansen JM, Hauge AW, Olesen J, et al. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010;30:1179–1186.
  • Asghar MS, Hansen AE, Amin FM, et al. Evidence for a vascular factor in migraine. Ann Neurol. 2011;4:635–645.
  • Recober A, Kuburas A, Zhang Z, et al. Role of calcitonin gene-related peptide in light aversive behavior: implications for migraine. J Neurosci. 2009;29:8798–8804.
  • Smillie SJ, King R, Kodji X, et al. An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress. Hypertension. 2014;63:1056–1062.
  • Schebesch KM, Herbst A, Bele S, et al. Calcitonin-gene related peptide and cerebral vasospasm. J Clin Neurosci. 2013;20:584–586.
  • Li J, Levick SP, DiPette DJ, et al. Alpha-calcitonin gene-related peptide is protective against pressure overload-induced heart failure. Regul Pept. 2013;185:20.
  • Homma S, Kimura T, Sakai S, et al. Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1: intravital microscopic observation and (31)P-MR spectroscopic studies. Life Sci. 2014;118:248–254.
  • Kang KT. Endothelium-derived relaxing factors of small resistance arteries in hypertension. Toxicol Res. 2014;30:141–148.
  • Gupta S, Mehrotra S, Villalón CM, et al. Characterisation of CGRP receptors in human and porcine isolated coronary arteries: evidence for CGRP receptor heterogeneity. Eur J Pharmacol. 2006;530:107–116.
  • Smillie SJ, Brain SD. Calcitonin gene-related peptide (CGRP) and its role in hypertension. Neuropeptides. 2011;45:93–104.
  • Li J, Carnevale KA, Dipette DJ, et al. Renal protective effects of α-calcitonin gene-related peptide in deoxycorticosterone-salt hypertension. Am J Physiol Renal Physiol. 2013;304:F1000–F8.
  • Avilés-Rosas VH, Rivera-Mancilla E, Marichal-Cancino BA, et. al. Olcegepant blocks neurogenic and non-neurogenic cgrpergic vasodepressor responses and facilitates noradrenergic vasopressor responses in pithed rats. Br J Pharmacol. 2017 Jul;174(13):2001-2014.
  • Wang Z, Martorell BC, Wälchli T, et al. Calcitonin gene-related peptide (CGRP) receptors are important to maintain cerebrovascular reactivity in chronic hypertension. PLoS One. 2015;10:e0123697.
  • Moskowitz MA, Sakas DE, Wei EP, et al. Postocclusive cerebral hyperemia is markedly attenuated by chronic trigeminal ganglionectomy. Am J Physiol. 1989;257:H1736–H9.
  • Sakas DE, Moskowitz MA, Wei EP, et al. Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures. Proc Natl Acad Sci USA. 1989;86:1401–1405.
  • Edvinsson L. Calcitonin gene-related peptide (CGRP) in cerebrovascular disease. ScientificWorldJournal. 2002;2:1484–1490.
  • Edvinsson L, Delgado-Zygmunt T, Ekman R, et al. Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage. J Cereb Blood Flow Metab. 1990;10:602–607.
  • Inoue T, Shimizu H, Kaminuma T, et al. Prevention of cerebral vasospasm by calcitonin gene-related peptide slow-release tablet after subarachnoid hemorrhage in monkeys. Neurosurgery. 1996;39:984–990.
  • Juul R, Edvinsson L, Gisvold SE, et al. Calcitonin gene-related peptide-LI in subarachnoid haemorrhage in man. Signs of activation of the trigemino-cerebrovascular system?. Br J Neurosurg. 1990;4:171–179.
  • Lei J, Zhu F, Zhang Y, et al. Transient receptor potential vanilloid Subtype 1 inhibits inflammation and apoptosis via the release of calcitonin gene-related peptide in the heart after myocardial infarction. Cardiology. 2016;134:436–443.
  • Gennari C, Fischer JA. Cardiovascular action of calcitonin gene-related peptide in humans. Calcif Tissue Int. 1985;37:581–584.
  • Saetrum Opgaard O, Hasbak P, de Vries R, et al. Positive inotropy mediated via CGRP receptors in isolated human myocardial trabeculae. Eur J Pharmacol. 2000;397:373–382.
  • Wang LH, Zhou SX, Li RC, et al. Serum levels of calcitonin gene-related peptide and substance P are decreased in patients with diabetes mellitus and coronary artery disease. J Int Med Res. 2012;40:134–140.
  • Gennari C, Nami R, Agnusdei D, et al. Improved cardiac performance with human calcitonin gene related peptide in patients with congestive heart failure. Cardiovasc Res. 1990;24:239–241.
  • Peng LM, Chen XP, Sun J, et al. Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP). Int J Clin Pharmacol Ther. 2012;50:701–711.
  • MaassenVanDenBrink A, Meijer J, Villalón CM, et al. Wiping out CGRP: potential cardiovascular risks. Trends Pharmacol Sci. 2016;37:779–788.
  • Zeller J, Poulsen KT, Sutton JE, et al. CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat. Br J Pharmacol. 2008;155:1093–1103.
  • Hou M, Xing H, Cai Y, et al. The effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor on migraine: a systematic review and meta-analysis. J Headache Pain. 2017;18:42.
  • Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377:2113–2122.
  • Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377:2123–2132.
  • Bigal ME, Walter S, Bronson M, et al. Cardiovascular and hemodynamic parameters in women following prolonged CGRP inhibition using LBR-101, a monoclonal antibody against CGRP. Cephalalgia. 2014;34:968–976.
  • Walter S, Alibhoy A, Escandon R, et al. Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide. MAbs. 2014;6:871–878.
  • Depre C, Antalik L, Starling A, et al. A randomized, double-blind, placebo-controlled study to evaluate the effect of erenumab on exercise time during a treadmill test in patients with stable Angina. Headache. 2018;58:715–723.
  • Tfelt-Hansen PC. Does sumatriptan cross the blood-brain barrier in animals and man? J Headache Pain. 2010;11:5–12.
  • Sakai Y, Dobson C, Diksic M, et al. Sumatriptan normalizes the migraine attack-related increase in brain serotonin synthesis. Neurology. 2008;70:431–439.
  • Evans DC, O’Connor D, Lake BG, et al. Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein. Drug Metab Dispos. 2003;31:861–869.
  • Negro A, Koverech A, Martelletti P. Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential. J Pain Res. 2018;11:515–526.
  • Lundblad C, Haanes KA, Grande G, et al. Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage. J Headache Pain. 2015;16:91.
  • Negro A, Lionetto L, Simmaco M, et al. CGRP receptor antagonists: an expanding drug class for acute migraine? Expert Opin Investig Drugs. 2012;21:807–818.
  • Giamberardino MA, Affaitati G, Curto M, et al. Anti-CGRP monoclonal antibodies in migraine: current perspectives. Intern Emerg Med. 2016;11:1045–1057.
  • Verheggen R, Bumann K, Kaumann AJ. BIBN4096BS is a potent competitive antagonist of the relaxant effects of alpha-CGRP on human temporal artery: comparison with CGRP(8–37). Br J Pharmacol. 2002;136:120–126.
  • Petersen KA, Birk S, Lassen LH, et al. The CGRP-antagonist, BIBN4096BS does not affect cerebral or systemic haemodynamics in healthy volunteers. Cephalalgia. 2005;25:139–147.
  • Lynch JJ, Shen YT, Pittman TJ, et al. Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8–37) on myocardial reactive hyperemic response in conscious dogs. Eur J Pharmacol. 2009;623:96–102.
  • Chan KY, Edvinsson L, Eftekhari S, et al. Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries. J Pharmacol Exp Ther. 2010;334:746–752.
  • Olesen J, Diener C, Husstedt IW, et al. BIBN 4096 BS clinical proof of concept study group. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med. 2004 [cited 2019 Apr 08];350:1104–1110. Available at: https://clinicaltrials.gov/show/NCT02198339
  • Ho TW, Mannix LK, Fan X, et al. Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology. 2008 [cited 2019 Apr 08];70:1304–1312. Available at https://clinicaltrials.gov/show/NCT00246337
  • Ho TW, Ferrari MD, Dodick DW, et al. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet. 2008 [cited 2019 Apr 08];372:2115–2123. Available at https://clinicaltrials.gov/show/NCT00442936
  • Connor KM, Shapiro RE, Diener HC, et al. Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology. 2009 [cited 2019 Apr 08];73:970–977. Available at https://clinicaltrials.gov/ct2/show/NCT00432237
  • Ho AP, Dahlof CG, Silberstein SD, et al. Randomized, controlled trial of telcagepant over four migraine attacks. Cephalalgia. 2010 [cited 2019 Apr 08];30:1443–1457. Available at https://clinicaltrials.gov/show/NCT00483704
  • Hewitt DJ, Martin V, Lipton RB, et al. Randomized controlled study of telcagepant plus ibuprofen or acetaminophen in migraine. Headache. 2011 [cited 2019 Apr 08];51:533–543. Available at https://clinicaltrials.gov/show/NCT00758836
  • Ho TW, Connor KM, Zhang Y, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology. 2014 [cited 2019 Apr 08];83:958–966. Available at https://clinicaltrials.gov/show/NCT00797667
  • Ho TW, Ho AP, Ge YJ, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for prevention of headache in women with perimenstrual migraine. Cephalalgia. 2016 [cited 2019 Apr 08];36:148–161. Available at https://clinicaltrials.gov/show/NCT01125774
  • Hewitt DJ, Aurora SK, Dodick DW, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia. 2011 [cited 2019 Apr 08];31:712–722. Available at https://clinicaltrials.gov/show/NCT00712725
  • Diener HC, Barbanti P, Dahlof C, et al. BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia. 2011 [cited 2019 Apr 08];31:573–584. Available at https://clinicaltrials.gov/show/NCT00751803
  • Study to Evaluate the PK of BMS-927711 in Patient With Migraine During Acute Migraine and Non-migraine Condition. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/show/NCT01445067
  • Marcus R, Goadsby PJ, Dodick D, et al. BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia. 2014 [cited 2019 Apr 08];34:114–125. . Available at: https://clinicaltrials.gov/show/NCT01430442
  • Safety and efficacy study in adult subjects with acute migraines. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/show/NCT03235479
  • Trial in Adult Subjects With Acute Migraines. [ cited 08 April 2019]. Available at https://clinicaltrials.gov/show/NCT03461757
  • Open label safety study in acute treatment of migraine. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/show/NCT03266588
  • Li CC, Dockendorf M, Kowalski K, et al. Population PK analyses of Ubrogepant (MK-1602), a CGRP receptor antagonist: enriching in-clinic plasma pk sampling with outpatient dried blood spot sampling. J Clin Pharmacol. 2017 [cited 2019 Apr 08].;58(3):294–303. Available at: https://clinicaltrials.gov/show/NCT01657370
  • Voss T, Lipton RB, Dodick DW, et al. A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. Cephalalgia. 2016 [cited 2019 Apr 08];36:887–898. Available at: https://clinicaltrials.gov/show/NCT01613248
  • Efficacy, safety, and tolerability of oral ubrogepant in the acute treatment ofmigraine. [ cited 2019 March 19]. Available at https://clinicaltrials.gov/show/NCT02867709
  • Efficacy, safety, and tolerability study of oral ubrogepant in the acute treatment of migraine. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/show/NCT02828020
  • An extension study to evaluate the long-term safety and tolerability of ubrogepant in the treatment of migraine. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/show/NCT02873221
  • Efficacy, Safety, and Tolerability of Multiple Dosing Regimens of Oral AGN-241689 in Episodic Migraine Prevention. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/show/NCT02848326. .
  • Allergan. Allergan’s Oral CGRP Receptor antagonist atogepant demonstrates robust efficacy and safety in episodic migraine prevention in a Phase 2b/3 Clinical Trial. [ cited 2019 April 08]. Available at: https://www.allergan.com/News/News/Thomson-Reuters/Allergan-s-Oral-CGRP-Receptor-Antagonist-Atogepant.
  • Schuster NM, Rapoport AM. Calcitonin gene-related peptide-targeted therapies for migraine and cluster headache: a review. Clin Neuropharmacol. 2017;40:169–174.
  • Luo G, Chen L, Conway CM, et al. Discovery of (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H cyclohepta[b]pyri din-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (BMS-927711): an oral calcitonin generelated peptide (CGRP) antagonist in clinical trials for treating migraine. J Med Chem. 2012;55:10644–10651.
  • Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine. [ cited 2019 April 08]. Available at: https://clinicaltrials.gov/ct2/show/NCT02605174?term=NCT02605174&rank=1
  • Mahmoud AN, Mentias A, Elgendy AY, et al. Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects. BMJ Open. 2018;8:e020498.
  • Martin VT, Goldstein JA. Evaluating the safety and tolerability profile of acute treatments for migraine. Am J Med. 2005;118:36S–44S.
  • Lipton RB, Reed ML, Kurth T, et al. Framingham-based cardiovascular risk estimates among people with episodic migraine in the US Population: results from the American Migraine Prevalence and Prevention (AMPP) study. Headache. 2017;57:1507–1521.
  • Barra S, Lanero S, Madrid A, et al. Sumatriptan therapy for headache and acute myocardial infarction. Expert Opin Pharmacother. 2010;11:2727–2737.
  • Winsvold BS, Hagen K, Aamodt AH, et al. Headache, migraine and cardiovascular risk factors: the HUNT study. Eur J Neurol. 2011;18:504–511.
  • Hall GC, Brown MM, Mo J, et al. Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004;62:563–568.
  • Bigal ME, Golden W, Buse D, et al. Triptan use as a function of cardiovascular risk. A population-based study. Headache. 2010;50:256–263.
  • Färkkilä M, Diener HC, Géraud G, et al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol. 2012;11:405–413.
  • Tepper SJ. Anti-Calcitonin Gene-Related Peptide (CGRP) therapies: update on a previous review after the American headache society 60th scientific meeting, San Francisco, June 2018. Headache. 2018;58(Suppl 3):276–290.
  • Yadav S, Yadav YS, Goel MM, et al. Calcitonin gene- and parathyroid hormone-related peptides in normotensive and preeclamptic pregnancies: a nested case-control study. Arch Gynecol Obstet. 2014;290(5):897–903.
  • Reuter U. A review of monoclonal antibody therapies and other preventative treatments in migraine. Headache. 2018;58(suppl 1):48–59.
  • Dong Y, Betancourt A, Chauhan M, et al. Pregnancy increases relaxation in human omental arteries to the CGRP family of peptides. Biol Reprod. 2015;93:134.
  • Fei X, Hongxiang Z, Qi C, et al. Maternal plasma levels of endothelial dysfunction mediators including AM, CGRP, sICAM-1 and tHcy in pre-eclampsia. Adv Clin Exp Med. 2012;21:573–579.
  • Negro A, Delaruelle Z, Ivanova TA, et al. European headache federation school of advanced studies (EHF-SAS). Headache and pregnancy: a systematic review. J Headache Pain. 2017;18:106.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.