Anti-CGRP Pharmacokinetics Point to a Migraine Site Outside the Blood–Brain Barrier
- A review tracing neurogenic inflammation from early neurophysiology to CGRP and today's anti-CGRP antibodies and oral receptor antagonists.
- It argues that anti-CGRP drug PK and the paracrine action of CGRP suggest headache arises in a spatially limited microenvironment outside the blood–brain barrier.
- That milieu comprises CGRP-containing C-fibre nociceptor endings and neighbouring cells including other nerve fibres.
💡 Points Based on the abstract
This is a good example of using drug PK as evidence about site of action: large antibodies that barely cross the barrier still work, which constrains where the target can sit. It is inferential, though, and small-molecule gepants that do reach the CNS are not cleanly separable from it. The practical use is for design: a peripheral-restricted mechanism argues against paying a CNS-penetration tax on the next migraine compound.
📄 Paper · British Journal of Pharmacology ↗ The role of neurogenic inflammation and CGRP in migraine headache