Pharmacokinetics and pharmacodynamics of new acute treatments for migraine

ABSTRACT

Introduction: Recommended medications for the acute treatment of migraine encompass triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), and analgesics. While it is true that triptans have been the first successful mechanism-driven treatment in the field, recently, new targets involved in migraine pathogenesis have emerged and new drug classes have been studied for migraine attack therapy.

Areas covered: Pharmacodynamics and pharmacokinetics of the new acute treatments of migraine (i.e. ditans, gepants, and glutamate receptor antagonists), considering also marketed drugs in new formulations and administration routes.

Expert opinion: Research on the administration routes of marketed drugs was performed in order to improve, in accordance with basic pharmacokinetics parameters, the speed of action of these medications. Similar to the triptans, the new acute treatments are migraine-specific medications, acting on the trigeminovascular system, albeit with different mechanisms. Although available data do not conclusively indicate the superiority of a class over the others, the pharmacodynamics explains the peculiar tolerability and safety profile of different drug classes emerging from clinical trials. Further studies are needed to investigate the possibility of combining different drug classes to optimize the clinical response and the potential role of the novel drugs in medication-overuse headache.

KEYWORDS:

• Migraine
• acute treatment
• lasmiditan
• gepants
• CGRP receptor antagonists
• glutamate receptor antagonists; 5-HT1F receptor agonists; ditans; nonsteroidal anti-inflammatory drugs; triptans

Article highlights

• Triptans are the gold standard for the acute migraine treatment but have class contraindications that limit their use in patients with cardiovascular diseases.

• The last decades of basic and clinical research have made it possible to improve the formulation of drugs already available and to develop new classes of drugs directed against prominent targets in the migraine pathophysiology, such as 5-HT_1F, CGRP and glutamate receptors.

• 5-HT_1F receptor agonists, CGRP receptor antagonists and glutamate receptor antagonists do not cause vasoconstriction, making those classes of drugs safe for patients with migraine who cannot use triptans.

• Lasmiditan has proven to be effective and well tolerated in the acute treatment of migraine in patients with high cardiovascular risk, and, in the light of the forthcoming drug application, insights on its pharmacokinetic profile should be made available from Phase 1 studies.

• The data available to date indicate that ditans, gepants and glutammate receptor antagonists are similarly effective and in some cases superior to triptans.

This box summarizes key points contained in the article.

Declaration of interest

A Negro received speaking Honoraria from Allergan and Novartis in 2018. C Lupi received congress sponsorship from Teva in 2018. S Benemei acted as a consultant for IBSA in 2018. S Guerzoni received sponsorship from Allergan and Novartis in 2018. L Pellesi received congress sponsorship from Allergan and Novartis in 2018. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.