Biochemistry & Pharmacology: Open Access
Open Access

CGRP in Migraine Treatment: Advances in Small-Molecular Antagonists and Monoclonal Antibodies for Effective Pain Management

Maiken Hadas^{* *}Correspondence: Maiken Hadas, Department of Pharmacology, University of Auckland, Auckland, New Zealand, Email:

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About the Study

Migraine therapy has advanced significantly with novel pharmacological approaches that aim to improve efficacy, reduce side effects, and provide personalized treatment options. These advances have been managing by a deeper understanding of migraine pathophysiology, including the roles of Calcitonin Gene-Related Peptide (CGRP), serotonin receptors, ion channels, and other neuroinflammatory pathways. Traditional migraine treatments, such as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and triptans, while effective for many, do not work for all patients and may be associated with significant side effects or contraindications.

CGRP is a neuropeptide that plays an important role in the transmission of pain and is involved in the dilation of blood vessels during a migraine attack. The discovery that CGRP levels are elevated during migraine attacks led to the development of CGRP receptor antagonists, which have shown efficacy in preventing and treating acute migraines. These antagonists work by blocking the binding of CGRP to its receptor, thereby reducing pain and other migraine symptoms. Small-molecule CGRP receptor antagonists, known as gepants, have emerged as a viable alternative to triptans, especially for patients who cannot tolerate or are contraindicated for triptan use. Unlike triptans, which cause vasoconstriction and may not be suitable for patients with cardiovascular conditions, gepants do not induce vasoconstriction and are considered safer for a broader patient population.

Another approach in migraine therapy involves monoclonal antibodies targeting CGRP or its receptor. These antibodies are designed for long-term prevention of migraines and are administered through subcutaneous or intravenous injection. They have demonstrated significant reductions in the frequency of migraine attacks in clinical trials and are associated with a favorable safety profile. The longer half-life of monoclonal antibodies allows for less frequent dosing, which improves patient compliance and convenience. Furthermore, they provide a targeted approach that minimizes systemic side effects compared to traditional oral medications.

In addition to CGRP-based therapies, serotonin receptor agonists continue to be an area of exploration. The role of serotonin in migraine pathophysiology has been established for many years, particularly the 5-Hydroxy Tryptamine receptor 1B (5-HT1B) and 5-Hydroxy Tryptamine receptor 1D (5-HT1D), which are targeted by triptans. Newer therapies are being developed to target other serotonin receptors, such as the 5-HT1F receptor. Agonists of the 5-HT1F receptor, called ditans, provide a novel mechanism of action that does not involve vasoconstriction, unlike triptans. This makes them a potentially safer option for patients with cardiovascular risk factors who experience migraines. Ditans act centrally to inhibit trigeminal nerve activation, which is a key component in migraine pathogenesis.

Ion channels play an important role in the excitability of neurons and are involved in the generation and propagation of migrainerelated pain signals. The sodium and calcium channels, in particular, have been implicated in migraine pathophysiology. Drugs that selectively target these channels can modulate neuronal excitability and reduce the frequency and severity of migraine attacks. One such approach involves the development of selective inhibitors of voltage-gated sodium channels that are preferentially expressed in pain pathways. These inhibitors are designed to block the abnormal neuronal firing associated with migraine without affecting normal neuronal function, thereby reducing the potential for side effects. Certain potassium channel openers can stabilize neuronal membranes and prevent excessive neuronal firing, which is thought to contribute to migraine attacks. This strategy is particularly attractive because it targets the fundamental neuronal mechanisms underlying migraine, providing a potential treatment option that could benefit patients who do not respond to other therapies. Neuroinflammation is increasingly recognized as a major component in migraine development, and this has increased interest about anti-inflammatory treatment modalities.