Migraine in the triptan era: progresses achieved, lessons learned and future developments

Abstract

-Triptans, serotonin 5-HT 1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine. This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. Herein we first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We then review the class of the triptans -mechanism of action and clinical evidence. We close by briefly discussing the class of CGRP receptor antagonists, which is currently being developed for the acute treatment of migraine.Key WoRDs: migraine, triptans, CGRP antagonists, emerging drugs.Migrânea na era dos triptanos: progressos alcançados, lições aprendidas e desenvolvimentos futuros resumo -os triptanos, agonistas serotoninérgicos 5-HT 1B/1D , revolucionaram o tratamento da migrânea promovendo pesquisas que evidenciaram aspectos da anatomia, fisiologia e farmacologia molecular deste tipo prevalente de cefaléia primária. esse conhecimento, por sua vez vem estimulando ainda mais a descoberta de novos mecanismos de ação para drogas anti-migranosas. Assim, é oportuno rever de forma crítica, os maiores avanços na ciência das cefaléias ocorridos durante a era dos triptanos. Inicialmente reveremos e conceituaremos alguns dos progressos obtidos nesta fase seguido de uma revisão profunda dos mecanismos de ação e evidências clínicas para o uso desta classe de fármacos. Finalmente, discutiremos a nova classe dos antagonistas dos receptores do peptideo geneticamente relacionado à calcitonina (CGRP) atualmente em desenvolvimento. Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms 1 . Attempts to alleviate the suffering caused by migraine span millennia and encompass treatments as primitive as trepanation of the skull, to increasingly specific medications that act on receptor subtypes implicated in the pathophysiology of migraine 2 . Triptans, serotonin 5-HT 1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine 3 . This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. To do so, we divided this views and reviews in two main components. We first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We focus on selective themes, and for each, we briefly discuss the established concept (status quo), as well as the evolving knowledge on the area. We then review the class of the triptans -mechanism of action an...

Chemical Mediators of Migraine: Preclinical and Clinical Observations

“…When compared, most of the triptans demonstrate a similar therapeutic gain when administered at doses recommended by manufacturer, 61 although s.c. sumatriptan has the highest therapeutic efficacy (For a full review of the efficacy and tolerability of all triptans, the reader is referred to previously published reviews as this is beyond the scope of the current manuscript. See Loder, Bigal et al, and Ramadan et al 61‐63 …”

Sumatriptan inhibition of N-type calcium channel mediated signaling in dural CGRP terminal fibres

“…The serotonin 5-HT 1 receptor agonist sumatriptan and the other so-called triptans are selective and effective therapies for the acute treatment of migraine pain (Bigal et al, 2009; Moskowitz and Cutrer, 1993; Sprenger and Goadsby, 2009; Tfelt-Hansen et al, 2000; Tfelt-Hansen and Koehler, 2011). However, despite the success of the triptans in the clinical setting, the anatomical locus of their antimigraine activity remains unresolved, and both peripheral and central nervous system sites of action are likely (Ahn and Basbaum, 2005; Akerman et al, 2011; Bartsch et al, 2004; Durham and Russo, 2002; Humphrey and Feniuk, 1991; Lambert, 2010; Levy et al, 2004; Mehrotra et al, 2008; Tfelt-Hansen, 2010).…”

Ризатриптан У Боротьбі З Симптомами Мігрені

“…Развиваемое им антимигренозное действие связывают с тремя основными механизмами: сужением менинге-альных сосудов, подавлением нейрогенного воспале-ния, уменьшением проведения боли [17][18][19].…”

“…Наконец, стимуляция 5-HT 1D -рецепторов ингибирует синаптическую транс-миссию (например, за счет угнетения высвобождения глутамата) от первичных ко вторичным сенсорным ней-ронам в тригеминоцервикальном комплексе, что ведет к уменьшению проведения боли. После перорального приема [19] ризатриптан бы-стро всасывается, и максимальная концентрация в плазме крови (T max ) достигается менее чем через 1 ч. Биодоступность составляет 40 %. Для сравнения, T max у суматриптана достигается через 2 ч, биодоступность составляет 14 %.…”