Abstract
The role of calcitonin gene-related peptide (CGRP) and its receptor have played an important role in migraine for the last decades due to development of therapies that target their receptors at the trigeminal pain system, aiming at prevention or relief of acute migraine attacks. At first, CGRP receptor antagonists, called gepants have demonstrated appropriate effectiveness. In addition, they did not cause vasoconstriction, one of the drawbacks of triptans. However, their use had to be discontinued due to the risk of liver toxicity. Humanized monoclonal antibodies towards CGRP and the CGRP receptor have been developed as an alternative approach to block CGRP transmission. Still, there are some questions not fully answered as where CGRP and its receptor are located, how they influence the mechanisms of migraine attacks and if the blood brain barrier has any sort of importance. There is still much to learn about CGRP and migraine pathophysiology, especially its anatomical target sites and anti-CGRP agents. This paper presents a review of CGRP, including a brief history, focusing in CGRP mechanism, updates and future treatments.
Highlights
Migraine is one of the oldest known diseases
For the treatment of these conditions, calcitonin gene-related peptide (CGRP) and its receptor have gained an important field in the last decades, which is the focus of this article
AMY1 was found in rats trigeminal ganglion, it appears to have a lesser role as is not blocked by drugs that target the CGRP receptor.[27]
Summary
Migraine is one of the oldest known diseases. The first report of migraine treatment comes from Egyptian medicine, about 4,000 years ago (Migraine - paradigm shift). The treatment of migraine has evolved over the years and, nowadays, molecular therapies have assumed an important role in this disease[1]. Trials involving anti-CGRP antibodies were developed, the main target of which was the use of medications for the prophylaxis of migraine attacks (galcanezumab, eptinezumab, fremanezumab, erenumab). It was only in 2018, 36 years after the description of the CGRP by Amara et al.[11] that the first drug, erenumab, was approved for use in the prevention of episodic migraine (
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