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. This evidence concerns the gene ADCYAP1 and migraine disorder.