Top

Published in:

Open Access 01-04-2018 | Review

Targeted 5-HT_1F Therapies for Migraine

Author: Marta Vila-Pueyo

Published in: Neurotherapeutics | Issue 2/2018

Abstract

Migraine is a common neurological disease characterised by the presence of attacks of unilateral, severe head pain accompanied by other symptoms. Although it has been classified as the sixth most disabling disorder, the available therapeutic options to treat this condition have not progressed accordingly. The advance in the development of 5-HT₁ receptor agonists for migraine, including 5-HT_1B/D and 5-HT_1F receptor agonists, has meant a major step forward towards the progression of a better treatment for migraine. Triptans have a limited efficacy, and their effect on vasoconstriction makes them unsafe for patients with cardiovascular and/or cerebrovascular diseases. Therefore, novel effective antimigraine treatments without cardiovascular effects are required, such as selective 5-HT_1F receptor agonists (ditans). Lasmiditan has much higher affinity for the 5-HT_1F receptor than for the vasoconstrictor 5-HT_1B receptor. This has been confirmed in preclinical studies performed to date, where lasmiditan showed no effect on vasoconstriction, and in clinical trials, where healthy individuals and patients did not report cardiac events due to treatment with lasmiditan, although it should be confirmed in larger cohorts. Lasmiditan crosses the blood-brain barrier and may act both centrally and peripherally on 5-HT_1F receptors expressed on trigeminal neurons. It is a well-tolerated compound that does not induce major adverse events. Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk. This review will focus on the characterisation of 5-HT₁ receptor agonists and their effects as migraine therapies.

Available only for authorised users

ICHD The International Classification of Headache Disorders, 3rd edition (beta version).Cephalalgia, 2013. 33(9): p. 629–808.CrossRef

Diener, H.C. and D.W.Dodick, Headache research in 2015: progress in migraine treatment. Lancet Neurol, 2016. 15(1): p. 4–5.CrossRefPubMed

Sicuteri, F., Headache as possible expression of deficiency of brain 5-hydroxytryptamine (central denervation supersensitivity).Headache, 1972. 12(2): p. 69–72.CrossRefPubMed

Pithadia, A.B. and S.M.Jain, 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials.J Clin Med Res, 2009. 1(2): p. 72–80.PubMedPubMedCentral

Lanfumey, L. and M. Hamon, 5-HT1 receptors.Curr Drug Targets CNS Neurol Disord, 2004. 3(1): p. 1–10.CrossRefPubMed

Siegel, G.A., BW; Albers, RW; Fisher, SK; Uhler, MD, Basic Neurochemistry: Molecular, cellular and medical aspects (6th edition). 1999: Lippincott - Raven.

Baxter, G., et al., 5-HT2 receptor subtypes: a family re-united?Trends Pharmacol Sci, 1995. 16(3): p. 105–10.CrossRefPubMed

Middlemiss, D.N. and P.H.Hutson, The 5-HT1B receptors.Ann N Y Acad Sci, 1990. 600: p. 132–47; discussion 347-48.CrossRefPubMed

Tfelt-Hansen, P.C. and P.J. Koehler, History of the use of ergotamine and dihydroergotamine in migraine from 1906 and onward.Cephalalgia, 2008. 28(8): p. 877–86.CrossRefPubMed

10.

Saper, J.R. and S.Silberstein, Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine.Headache, 2006. 46 Suppl 4: p. S171–81.CrossRefPubMed

11.

Silberstein, S.D. and D.C.McCrory, Ergotamine and dihydroergotamine: history, pharmacology, and efficacy.Headache, 2003. 43(2): p. 144–66.CrossRefPubMed

12.

Silberstein, S.D., Methysergide.Cephalalgia, 1998. 18(7): p. 421–35.CrossRefPubMed

13.

Silberstein, S.D., Preventive treatment of migraine: an overview.Cephalalgia, 1997. 17(2): p. 67–72.CrossRefPubMed

14.

Koehler, P.J. and P.C.Tfelt-Hansen, History of methysergide in migraine.Cephalalgia, 2008. 28(11): p. 1126–35.CrossRefPubMed

15.

Ramirez Rosas, M.B., et al., Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs.Expert Opin Pharmacother, 2013. 14(12): p. 1599–610.CrossRefPubMed

16.

Dahlof, C. and A. Maassen Van Den Brink, Dihydroergotamine, ergotamine, methysergide and sumatriptan—basic science in relation to migraine treatment.Headache, 2012. 52(4): p. 707–14.CrossRefPubMed

17.

Ferrari, M.D., Sumatriptan in the treatment of migraine.Neurology, 1993. 43(6 Suppl 3): p. S43–7.PubMed

18.

Macone, A.E. and M.D.Perloff, Triptans and migraine: advances in use, administration, formulation, and development.Expert Opin Pharmacother, 2017. 18(4): p. 387–397.CrossRefPubMed

19.

Barbanti, P., et al., Serotonin receptor targeted therapy for migraine treatment: an overview of drugs in phase I and II clinical development.Expert Opin Investig Drugs, 2017. 26(3): p. 269–277.CrossRefPubMed

20.

MaassenVanDenBrink, A., et al., Coronary side-effect potential of current and prospective antimigraine drugs.Circulation, 1998. 98(1): p. 25–30.CrossRefPubMed

21.

Tfelt-Hansen, P.C. and J. Olesen, The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials.J Headache Pain, 2012. 13(4): p. 271–5.CrossRefPubMedPubMedCentral

22.

Tfelt-Hansen, P.C., et al., Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs.Expert Opin Investig Drugs, 2014. 23(3): p. 375–85.CrossRefPubMed

23.

Reuter, U., H. Israel, and L. Neeb, The pharmacological profile and clinical prospects of the oral 5-HT1F receptor agonist lasmiditan in the acute treatment of migraine.Ther Adv Neurol Disord, 2015. 8(1): p. 46–54.CrossRefPubMedPubMedCentral

24.

Limmroth, V., et al., Features of medication overuse headache following overuse of different acute headache drugs.Neurology, 2002. 59(7): p. 1011–4.CrossRefPubMed

25.

Villalon, C.M., et al., Migraine: pathophysiology, pharmacology, treatment and future trends.Curr Vasc Pharmacol, 2003. 1(1): p. 71–84.CrossRefPubMed

26.

Lipton, R.B., M.E. Bigal, and P.J. Goadsby, Double-blind clinical trials of oral triptans vs other classes of acute migraine medication—a review.Cephalalgia, 2004. 24(5): p. 321–32.CrossRefPubMed

27.

Amlaiky, N., et al., Isolation of a mouse “5HT1E-like” serotonin receptor expressed predominantly in hippocampus.J Biol Chem, 1992. 267(28): p. 19761–4.PubMed

28.

Johnson, K.W., et al., 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs.Neuroreport, 1997. 8(9–10): p. 2237–40.CrossRefPubMed

29.

Barnes, N.M. and T.Sharp, A review of central 5-HT receptors and their function.Neuropharmacology, 1999. 38(8): p. 1083–152.CrossRefPubMed

30.

Adham, N., et al., Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.Proc Natl Acad Sci U S A, 1993. 90(2): p. 408–12.CrossRefPubMedPubMedCentral

31.

Fugelli, A., C. Moret, and G. Fillion, Autoradiographic localization of 5-HT1E and 5-HT1F binding sites in rat brain: effect of serotonergic lesioning.J Recept Signal Transduct Res, 1997. 17(4): p. 631–45.CrossRefPubMed

32.

Lucaites, V.L., et al., [3H]LY334370, a novel radioligand for the 5-HT1F receptor. II. Autoradiographic localization in rat, guinea pig, monkey and human brain.Naunyn Schmiedebergs Arch Pharmacol, 2005. 371(3): p. 178–84.CrossRefPubMed

33.

Jeong, H.J., et al., Sumatriptan inhibits synaptic transmission in the rat midbrain periaqueductal grey.Mol Pain, 2008. 4: p. 54.CrossRefPubMedPubMedCentral

34.

Bonnin, A., et al., Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development.Neuroscience, 2006. 141(2): p. 781–94.CrossRefPubMed

35.

Classey, J.D., T. Bartsch, and P.J. Goadsby, Distribution of 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor expression in rat trigeminal and dorsal root ganglia neurons: relevance to the selective anti-migraine effect of triptans.Brain Res, 2010. 1361: p. 76–85.CrossRefPubMed

36.

Ma, Q.P., Co-localization of 5-HT(1B/1D/1F) receptors and glutamate in trigeminal ganglia in rats.Neuroreport, 2001. 12(8): p. 1589–91.CrossRefPubMed

37.

Ahn, S.K., et al., Colocalization of 5-HT1F receptor and calcitonin gene-related peptide in rat vestibular nuclei.Neurosci Lett, 2009. 465(2): p. 151–6.CrossRefPubMed

38.

Ahn, S.K., et al., Colocalization of 5-HT1F receptor and glutamate in neurons of the vestibular nuclei in rats.Neuroreport, 2009. 20(2): p. 111–5.CrossRefPubMed

39.

Vila-Pueyo M, Strother L., PageK, LoaraineH, KovalchinJ, GoadsbyPJ, HollandPR, Lasmiditan inhibits trigeminovascular nociceptive transmission.Cephalalgia, 2016. 36: p. 152.

40.

Bouchelet, I., et al., Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels.Mol Pharmacol, 1996. 50(2): p. 219–23.PubMed

41.

Castro, M.E., et al., Differential distribution of [3H] sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord.Neuropharmacology, 1997. 36(4–5): p. 535–42.CrossRefPubMed

42.

Bouchelet, I., et al., No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery.Br J Pharmacol, 2000. 129(3): p. 501–8.CrossRefPubMedPubMedCentral

43.

Olesen, J., 5-Hydroxyptryptamine 1F (5-HT1F) receptor agonism. A possible new treatment principle for acute migraine attacks.Cephalalgia, 2010. 30(10): p. 1157–8.CrossRefPubMed

44.

Rizzoli, P.B., Emerging therapeutic options for acute migraine: focus on the potential of lasmiditan.Neuropsychiatr Dis Treat, 2014. 10: p. 547–52.CrossRefPubMedPubMedCentral

45.

Goadsby, P.J., The vascular theory of migraine--a great story wrecked by the facts.Brain, 2009. 132(Pt 1): p. 6–7.CrossRefPubMed

46.

Goadsby, P.J., et al., Pathophysiology of Migraine: A Disorder of Sensory Processing.Physiol Rev, 2017. 97(2): p. 553–622.CrossRefPubMedPubMedCentral

47.

Akerman, S., M.Romero-Reyes, and P.R.Holland, Current and novel insights into the neurophysiology of migraine and its implications for therapeutics.Pharmacol Ther, 2017. 172: p. 151–170.CrossRefPubMed

48.

Puledda, F. and P.J.Goadsby, An Update on Non-Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine.Headache, 2017. 57(4): p. 685–691.CrossRefPubMed

49.

Nelson, D.L., et al., Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan.Cephalalgia, 2010. 30(10): p. 1159–69.CrossRefPubMed

50.

Kovalchin J, G.A., Zanelli E, Ings R, Mathers T, Lasmiditan acts specifically on the 5-HT1F receptors in the central nervous system. 2016.

51.

Rubio-Beltran E, K Haanes, Labastida A, de Vries R, Danser J, Michael G, Peter S, Kovalchin J, Villalon C, MaassenVanDenBrink A, Lasmiditan and sumatriptan: comparison of in vivo vascular constriction in the dog and in vitro contraction of human arteries. Cephalalgia, 2016. 36 (1S): p. 104.

52.

Labastida-Ramírez, A., Rubio-Beltrán E; Garrelds, IM; Haanes, KA; Chan, KY; Kovalchin, J; Johnson, KW; Danser, AH; Villalón, CM; MaassenVanDenBrink, A, Lasmiditan inhibits CGRP release in the mouse trigeminovascular system. Cephalalgia, 2017. 37(IS): p. 362.

53.

Pilgrim A, Dussault B., Rupniak N, White J, Mazur D, DiSanto AR, COL-144, an orally bioavailable selective 5-HT1F receptor agonist for acute migraine therapy, Cephalalgia. 2009. 29(1S): p. 24–25.

54.

Moskowitz, M.A. and R. Macfarlane, Neurovascular and molecular mechanisms in migraine headaches.Cerebrovasc Brain Metab Rev, 1993. 5(3): p. 159–77.PubMed

55.

Peroutka, S.J., Neurogenic inflammation and migraine: implications for the therapeutics.Mol Interv, 2005. 5(5): p. 304–11.CrossRefPubMed

56.

Ahn, A.H. and A.I. Basbaum, Where do triptans act in the treatment of migraine?Pain, 2005. 115(1–2): p. 1–4.CrossRefPubMedPubMedCentral

57.

Phebus, L.A., et al., Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine.Life Sci, 1997. 61(21): p. 2117–26.CrossRefPubMed

58.

Mitsikostas, D.D., M. Sanchez del Rio, and C. Waeber, 5-Hydroxytryptamine(1B/1D) and 5-hydroxytryptamine1F receptors inhibit capsaicin-induced c-fos immunoreactivity within mouse trigeminal nucleus caudalis.Cephalalgia, 2002. 22(5): p. 384–94.CrossRefPubMed

59.

Mitsikostas, D.D., et al., Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis.Eur J Pharmacol, 1999. 369(3): p. 271–7.CrossRefPubMed

60.

Shepheard, S., et al., Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370.Cephalalgia, 1999. 19(10): p. 851–8.CrossRefPubMed

61.

Goadsby, P.J. and J.D. Classey, Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F receptor inhibitory effects on trigeminal neurons with craniovascular input.Neuroscience, 2003. 122(2): p. 491–8.CrossRefPubMed

62.

Amrutkar, D.V., et al., mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system.Pain, 2012. 153(4): p. 830–8.CrossRefPubMed

63.

Database of privately and publicly funded clinical studies conducted around the world [online]. Available at: https://clinicaltrials.gov . [cited 2017 August].

64.

Capi, M., et al., Lasmiditan for the treatment of migraine.Expert Opin Investig Drugs, 2017. 26(2): p. 227–234.CrossRefPubMed

65.

Liefaard L, Drenth H., Pilgrim AJ, Dussault B, Rupniak N, DiSanto AR, White J, Prediction of therapeutically effective dose of COL-144 based on relationship between plasma concentrations and headache response. Cephalalgia, 2016. 29 (Supp 1) p. 24.

66.

Food-Effect Study in Healthy Subjects [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT02233296?term=lasmiditan&phase=0&rank=4 . [cited 2017 August].

67.

Absorption, Metabolism and Excretion of [14C]-Lasmiditan—Single Oral Dose Administration [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03040362?term=lasmiditan&phase=0&rank=1 . [cited 2017 August].

68.

Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan in Healthy Subjects [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03076970?term=lasmiditan&phase=0&rank=5 . [cited 2017 August].

69.

The Effects of Lasmiditan on Simulated Driving Performance-Healthy Volunteers [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03012334?term=lasmiditan&phase=0&rank=7 . [cited 2017 August].

70.

Study of Oral Lasmiditan in Subjects With Normal and Impaired Renal Function [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03009162?term=lasmiditan&phase=0&rank=3 . [cited 2017 August].

71.

Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Hepatic Function [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03040479?term=lasmiditan&phase=0&rank=6 . [cited 2017 August].

72.

A Study of Lasmiditan in Healthy Participants [online]. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03182920?term=lasmiditan&phase=0&rank=2 . [cited 2017 August].

73.

Ferrari, M.D., et al., Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan—a randomised proof-of-concept trial.Cephalalgia, 2010. 30(10): p. 1170–8.CrossRefPubMed

74.

A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT00384774?term=lasmiditan&phase=1&rank=2 . [cited 2017 August].

75.

Reuter U, P.A., Diener HC, Färkkilä M, Ferrari M for the European COL-144 investigators, COL-144: A Selective 5-HT1F Agonist For the Treatment of Migraine Attacks.2008.

76.

Farkkila, M., 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(5): p. 405–13.CrossRefPubMed

77.

Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT00883051?term=lasmiditan&phase=1&rank=1 . [cited 2017 August].

78.

Lasmiditan Compared to Placebo in the Acute Treatment of Migraine: (SAMURAI) [online]. Available at: https://clinicaltrials.gov/ct2/show/study/NCT02439320?term=lasmiditan&phase=2&rank=2 . [cited 2017 August].

79.

Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN) [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT02605174?term=lasmiditan&phase=2&rank=3 . [cited 2017 August].

80.

An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine (GLADIATOR) [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT02565186?term=lasmiditan&phase=2&rank=1 . [cited 2017 August].

81.

Raffaelli, B., et al., The safety and efficacy of the 5-HT 1F receptor agonist lasmiditan in the acute treatment of migraine.Expert Opin Pharmacother, 2017.

82.

SAMURAI results EHMTIC 2016 [online]. Available at: http://www.colucid.com/wp-content/uploads/2016/09/SAMURAI-Results-for-EHMTIC-2016-FINAL.pdf. [cited 2017 August].

83.

Lilly Announces Positive Results for Second Phase 3 Study of Lasmiditan for the Acute Treatment of Migraine [online]. Available at: https://investor.lilly.com/releasedetail.cfm?ReleaseID=1036101 . [cited 2017 October].

Title: Targeted 5-HT1F Therapies for Migraine
Author: Marta Vila-Pueyo
Publication date: 01-04-2018
Publisher: Springer International Publishing
Published in: Neurotherapeutics / Issue 2/2018
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI: https://doi.org/10.1007/s13311-018-0615-6

2024 ASCO Annual Meeting

Springer Medicine

Targeted 5-HT_1F Therapies for Migraine

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2018

Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections—a Nationwide, Population-Based Cohort Study in Taiwan

Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy—a Prospective Follow-Up

Non-Pharmacological Approaches for Migraine

Association of Herpes Viral Infections, Antiherpetic Therapy, and Dementia: Real or Alternative Fact?

Pilot Single-Blind Trial of AbobotulinumtoxinA in Oromandibular Dystonia

Targeted CGRP Small Molecule Antagonists for Acute Migraine Therapy