Telcagepant and topiramate are having the potential to become new treatment for migraine headache, according to a study in Lancet.
Although the triptan drugs provide effective relief from migraine for many patients, a substantial number of affected individuals do not respond to these compounds.
In a meta-analysis of migraine treatment with triptans, up to a third of all people with migraine and 40% of all migraine attacks did not respond to these drugs.
Triptans also cause a range of adverse effects.
Telcagepant, a calcitonin gene-related peptide receptor blocker,.represents a new class of antimigraine drugs, researchers claim.
Telcagepant exerts its effects by blocking receptors for the calcitonin-gene-related peptide at several sites in the trigeminal and central nervous systems, resulting in pain relief. During migraine attacks, CGRP binds to and activates CGRP receptors, which helps transmit pain impulses. Telcagepant blocks CGRP from binding to its receptors within the nervous system and thereby is believed to inhibit the transmission of the pain signals that lead to migraine headaches.
Telcagepant does not cause vasoconstriction, a major limitation in the use of triptans.
Comparisons with triptans in clinical trials for acute treatment of migraine attacks revealed clinical effects similar to those of triptans but better than those of placebo.
Telcagepant seems to be one such promising compound, although further investigation is warranted to firmly establish its role. Whether CGRP-receptor antagonists can be combined with triptans to give more effective therapy and whether they will be of value in patients who do not respond to a triptan, are questions need to be explored further.
Also, effectiveness of triptans in children has not been proven.
Telcagepant is in the final stages of development by Merck.
In June 2008, Merck & Co. announced that, in a Phase III clinical trial, telcagepant (formerly MK-0974) significantly improved relief of migraine pain and migraine-associated symptoms two hours after dosing compared to placebo. In addition, the efficacy results for telcagepant 300 mg were similar to the highest recommended dose of zolmitriptan, an approved migraine therapy, with a lower incidence of adverse events associated with telcagepant in this study.
However, Merck halted a phase IIa clinical trial studying telcagepant for the prophylaxis of episodic migraine was stopped in March 2009 after preliminary reports that the drug increases the hepatic liver enzyme alanine transaminase (AST) levels in 11 out of 660 randomized (double-blinded) study participants.
While telcagepant might provide hope for those who have a poor response to, or are unable to use, older drugs, topiramate could be an effective prophylactic, a drug to prevent a potential migraine attack, studies suggest.
In patients who need prophylaxis because of frequent attacks of migraine, topiramate is a first-line drug for migraine prevention in many countries.
Topiramate is generally safe and reasonably well tolerated. Data suggest that topiramate could aid reversion of chronic migraine to episodic migraine.
The introduction of topiramate has been the most important advance in migraine prophylaxis.
Although topiramate is an old drug, its use in migraine prophylaxis is a new indication, hence its inclusion in this New Drug Class paper, wrote the researchers Lars Edvinsson, MD, University Hospital, Lund, Sweden, and Mattias Linde, MD, Norwegian University of Science and Technology, and St Olavs Hospital, Trondheim, Norway.
“Topiramate is a first-line migraine preventive drug in many countries and should especially be considered for adult patients who are overweight, or have epilepsy or a contraindication to beta-blockers,” the authors wrote
Since topiramate could reverse chronic migraine with or without drug overuse to episodic migraine, it can be an important drug for difficult cases.”
During migraine attacks, CGRP binds to and activates CGRP receptors, which helps transmit pain impulses. Telcagepant blocks CGRP from binding to its receptors within the nervous system and thereby is believed to inhibit the transmission of the pain signals that lead to migraine headaches.
Migraine is a disabling disorder of the brain that affects 35 million Americans, primarily women. Unlike a bad headache, migraines are characterized by attacks of intense, usually one-sided, throbbing head pain that can last from four to 72 hours. The pain associated with migraine is frequently accompanied by other symptoms, including nausea, vomiting and increased sensitivity to light and sound.