Current Prophylactic Medications for Migraine and Their Potential Mechanisms of Action

Abstract

A relatively high number of different medications is currently used for migraine prevention in clinical practice. Although these compounds were initially developed for other indications and differ in their mechanisms of action, some general themes can be identified from the mechanisms at play. Efficacious preventive drugs seem to either suppress excitatory nervous signaling via sodium and/or calcium receptors, facilitate GABAergic inhibition, reduce neuronal sensitization, block cortical spreading depression and/or reduce circulating levels of CGRP. We here review such mechanisms for the different compounds.

Cholinergic modulation inhibits cortical spreading depression in mouse neocortex through activation of muscarinic receptors and decreased excitatory/inhibitory drive

“…These are synergic effects that could be used in migraine therapy for inhibiting CSD and its consequences, and possibly in other pathological conditions in which spreading depolarizations are involved (Klass et al, 2018). Several drugs are used for migraine therapy in clinical practice, with different mechanisms that include decreased excitability of cortical circuits, modulation of neuronal plasticity, reduction of circulating levels of calcitonin generelated peptide (CGRP, a peptide released by nociceptors and implicated in migraine headache) and/or inhibition of cortical spreading depression (Ayata et al, 2006;Costa et al, 2013;Mantegazza et al, 2010;Sprenger et al, 2018). However, muscarinic agonists are not used in migraine treatment.…”

From transformation to chronification of migraine: pathophysiological and clinical aspects

“…Treatments that have proved efficacy in migraine patients, have been shown to prevent mechanical hyperalgesia in animal models [113,131]. For example, botulinum toxin could act peripherally inhibiting the release of a variety of neurotransmitters which are known to be key signaling molecules in CM including CGRP [132,133], so animal pre-treatment with botulinum toxin can prevent mechanical sensitization inhibiting mechanical nociception in peripheral trigeminovascular neurons [134]. For example, the mechanism of action of noninvasive vagus nerve stimulation for migraine treatment have also been investigated in the inflammatory soup model showing a decrease in periorbital sensitivity after de vagal stimulation [135].…”

The Use of Antioxidants in the Treatment of Migraine

“…Due to the reported drug intolerance and side effects, feverfew is not recommended as the first-line treatment drug in migraine prevention [100]. The most commonly reported side effects of feverfew are oral ulcers, gastrointestinal irritation, allergic reactions, and rebound headache [99].…”