Recent Advancements in Anti-Migraine Drug Research: Focus on Attempts to Decrease Neuronal Hyperexcitability

Abstract

Migraine is a painful, sometimes debilitating disorder, which is frequently associated with various neurological symptoms. Its prevalence in the population is higher than that of any other neurological disorders, thus the burden of this disease on society is considerable. Although the introduction of triptans nearly two decades ago revolutionized the treatment of the disease there is still a huge unmet need regarding drugs with better properties. Formerly, migraine therapy primarily aimed at treating the pathological alterations of meningeal blood vessels that are thought to directly initiate a migraine headache attack. By now, it has been increasingly recognized by drug companies that abnormal neural function may be more important in the development of the disease and also in triggering an attack. Migraine is associated with an increased neuronal excitability and episodes of cortical spreading depression. Understanding the molecular mechanisms underlying the abnormal functioning of over-activated neuronal circuits may help to identify novel anti-migraine drug targets. Besides a general description of the pathophysiology and pharmacotherapy of migraine this review paper aims at discussing the possible drug targets through which migraine-related hyperexcitability and over-excitation can be attenuated. It will be shown how these new ideas appear in the recent patent literature.

Perivascular neurotransmitters: Regulation of cerebral blood flow and role in primary headaches

“…Neuronal hyperexcitability and over-activated neuronal circuits are considered functional abnormalities in migraine and believed to be important in triggering headache/migraine attacks. 186 More information on multiple internal and external headache triggers (e.g. sleep disturbance, stress, light, odors) can be found in thorough reviews by Ho et al 15 and Borkum.…”

Neurological perspectives on voltage-gated sodium channels

“…Migraine is treated with a wide range of drugs, including tryptans that, through their agonist effects on serotonin receptors, block the release of vasoactive neuropeptides such as CGRP. Other treatments include the use of non-steroidal anti-inflammatory drugs, anti-depressants and calcium channel blockers (Bolcskei et al , 2009). Epilepsy is a co-morbid condition of migraine.…”

“…It is important to note that use-dependent selective VGSC blockers, such as phenytoin and carbamazepine, have not been documented to be efficacious against migraine attacks (Rogawski and Loscher, 2004). Finally, intranasal application of the local anaesthetic and anti-arrhythmic compound lidocaine was reported to be an effective treatment for some refractory migraines (Kudrow et al , 1995; Bolcskei et al , 2009). …”

Development of Frovatriptan Succinate Microemulsion for Nasal Delivery: Optimization, in Vitro and in Vivo Evaluation

“…Migraine is a neurological disorder with intense, unilateral, throbbing, and pulsatile headache attacks that may last for 4-72 h and may be accompanied by anorexia, nausea, vomiting, photophobia, and/or phonophobia [8]. In connection with migraine, drugs used in treatment must be absorbed immediately for fast onset of action and high bioavailability.…”