Gepants for migraine treatment
Keywords:gepants, treatment, migraine
The pathophysiology of migraine is related to neurogenic inflammation due to activation and sensitization of the trigeminovascular pain pathway. Activation of the trigeminovascular system results in the release of various neuropeptides, including serotonin, calcitonin gene-related peptide (CGRP), and dopamine. Interrupting the sensitization process by suppressing CGRP is the basis of modern migraine treatment. Medications that inhibit the CGRP pathway can be used to treat migraine attacks and for migraine prophylaxis.
Two classes of drugs are used that directly inhibit CGRP function: monoclonal antibodies (mAbs) targeting CGRP and small molecule CGRP antagonists (gepants). Four mAbs targe ting CGRP are approved for migraine prophylaxis: the CGRP antagonists galcanezumab, fremanezumab, eptinezumab, and the CGRP receptor antagonist antibody erenumab. Because they are large molecules, they require parenteral (subcutaneous or intravenous) administration, which makes their long-term administration difficult. Small molecule CGRP receptor antagonists are effective in the treatment of migraine attacks and have a short (10 hours) half-life.
Some gepants can be used not only for the treatment of migraine attacks, but also for prevention. Three second-generation gepants are approved for the abortive or prophylactic treatment of migraine: ubrogepant, rimegepant and atogepant. Gepants suppress CGRP-induced vasodilation without causing
vasoconstriction, making them a preferred alternative in patients with contraindications to triptan therapy. Hepatotoxicity was not found, as with the first generation of gepants.
Gepants are recommended for the treatment of a migraine attack in the absence of effect from the treatment with two or more different triptans. There are no recommendations for when to administer them for migraine prophylaxis, but in clinical practice they are administered after failure of prophylaxis with at least two classes of other medications. Gepants have only been studied in episodic migraine, but it is suggested that they may be effective in chronic migraine and drug overuse headache.
In conclusion, gepants are a new class of drugs that show promise for both migraine attack treatment and migraine prevention.
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