Migraine: Pathophysiology, Pharmacology, Treatment and Future Trends

Abstract

Migraine treatment has evolved into the scientific arena, but it seems still controversial whether migraine is primarily a vascular or a neurological dysfunction. Irrespective of this controversy, the levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter, seem to decrease during migraine (with associated carotid vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation. The last decade has witnessed the advent of sumatriptan and second generation triptans (e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs, the 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the second-generation triptans have a higher oral bioavailability and longer plasma half-life. In line with the vascular and neurogenic theories of migraine, all triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and presynaptic inhibition of the trigeminovascular inflammatory responses implicated in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D (PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system without producing vasoconstriction. Nevertheless, PNU-142633 proved to be ineffective in the acute treatment of migraine, whilst LY344864 did show some efficacy when used in doses which interact with 5-HT1B receptors. Finally, although the triptans are effective antimigraine agents producing selective cranial vasoconstriction, efforts are being made to develop other effective antimigraine alternatives acting via the direct blockade of vasodilator mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors, inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully lead to fewer side effects.

Elastic liposomes as novel carriers: recent advances in drug delivery

“…A migraine is a neurological disease characterized with recurrent headache (typically existing for 4-72 h), accompanied with frequent nausea, headache, vomiting, photophobia, phonophobia, and gastric disturbances. 101,102 Triggering neuropeptides is responsible to produce painful inflammation in cranial vessels and the dura mater. 101 An episodic migraine is considered a precursor of chronic migraines.…”

“…101 An episodic migraine is considered a precursor of chronic migraines. 102 Thus, migraines could be progressive and necessitate sustained-release formulations for treatment of the disorder. Garg et al developed ELs to deliver the 5-HT1B agonist rizatriptan for transdermal sustained release, followed by in vivo activity in a mouse model using morphine (withdrawal-induced hyperalgesia model).…”

A Recent Review on Nasal Microemulsion for Treatment of CNS Disorder

“…Sumatriptan is rapidly but incompletely absorbed following oral administration and undergoes the first-pass metabolism, resulting in a low absolute bioavailability of 14% in humans [45]. The transport of Sumatriptan across the blood-brain barrier (BBB) is very poor [46].…”

Lipid levels and selected biomarkers of vascular changes in children with idiopathic headaches – a preliminary report

“…It is a significant health concern with complex and multi-faceted diagnostics and treatment. Vasospasm and accompanying ischemia play an important role in the primary headache pathophysiology [2]. Migraine is suggested to be one of the first signs of atherosclerosis and disorders in lipid metabolism.…”