Emerging pharmacological targets in migraine therapy: CGRP and beyond
Abstract
Migraine is a prevalent, complex, and disabling neurological disorder. Available treatments consist of repurposed drugs, with medication switching and treatment failure a common occurrence. Pathophysiological models have shifted from migraine being a primarily vascular disorder to a complex network disease encompassing cortical, hypothalamic, thalamic, brainstem, trigeminovascular, and meningeal structures. These areas are interconnected by cascades of multiple signalling transmitters and hormones. This review explores how these molecules may offer novel pharmacological targets for efficacious treatments tailored to the pathophysiology of migraine. Calcitonin gene-related peptide (CGRP) directed therapies include antagonists (“gepants”) and monoclonal antibodies. Both drug classes have shown promising effects in managing pain in acute migraine attacks and in prophylactically reducing headache frequency, even within treatment-resistant migraine populations. Animal studies have shown drugs targeting pituitary adenylate cyclase-activating polypeptide (PACAP) signalling to reduce meningeal vasodilation and chronic allodynia. PACAP ligand-directed monoclonal antibodies offer therapeutic promise in patients with treatment-resistant migraine; however, this evidence base is limited and requires further research. Amylin may offer a novel therapeutic target for migraine; however, currently no such therapies have been developed. Neurokinin receptor antagonists have so far shown little…
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