Rodent data involving radiolabelled PACAP identified a mere brain uptake of <0.07% for both its isoforms (i.e. PACAP-38 and PACAP-27) in rodents.41 Recent findings also cast further doubt on the therapeutic promise of PAC1 receptor antagonism, given a monoclonal antibody against the PAC1 receptor failed against placebo for migraine prevention in a phase II trial.42 Nonetheless, concerns with dosing, potency, and the possibility of alternative receptor splice variants, cannot be excluded as reasons for failure. Here, ADCYAP1R1 is linked to migraine disorder.