Targeting the PACAP-38 pathway is an emerging therapeutic strategy for migraine prevention

Figures & data

Table 1. Competitive environment for PACAP antagonists intended to prevent migraine.

Compound	Company	Structure	Indication	Mechanism of action	Stage of development
AMG 301	Amgen Inc.	Monoclonal antibody	Migraine prevention	Inhibitor of the PAC1 receptor	Terminated
Lu AG09222	Lundbeck	Monoclonal antibody	Migraine prevention	Inhibitor of PACAP peptide	Phase II
LY3451838	Eli Lilly	Monoclonal antibody	Migraine prevention	Inhibitor of PACAP peptide	Phase II

Figure 1. Hypothesized mechanisms of PACAP-induced migraine. The trigeminovascular activation results in sensory release of pituitary adenylate cyclase-activating peptide-38 (PACAP-38) that dilates intracranial and dural arteries and promotes the increase in extracellular potassium by activating the ATP-sensitive potassium channels (K_ATP channels) (a). PACAP-38 activates the Mas-related G-protein coupled receptor X2 (MRGPX2) on meningeal mast cells to release various neuroinflammatory mediators in close proximity to meningeal afferent fibers (b). Created with BioRender.com.