CGRP blockers in migraine therapy: where do they act?
Calcitonin gene-related peptide (CGRP) is expressed throughout the CNS and peripheral nervous system, consistent with control of vasodilatation, nociception, motor function, secretion and olfaction. AlphaCGRP is prominently localized in primary afferent C and Adelta fibres of spinal and trigeminal ganglia. Activation of the trigeminal nerve results in antidromic release of CGRP, acting through a CGRP1 receptor. Antagonists of CGRP1 receptors reduce signalling in the trigeminovascular pathway at multiple sites, putatively inside the blood-brain barrier. Other ways of interacting with CGRP mechanisms have appeared limiting the availability of CGRP in the circulation with a specific CGRP antibody or with a CGRP-binding RNA-Spiegelmer. Either way reduces neurogenic inflammation and attenuates signalling within the trigeminovascular pathway. Specific CGRP receptor blockade has been shown to reduce the effect of released CGRP and to abort acute migraine attacks. The novel approach of reducing available CGRP is limited by the blood-brain barrier; its usefulness may be more as prophylaxis rather than as acute treatment of migraine.
Edvinsson
L
L
Department of Medicine, Institute of Clinical Sciences, Lund University Hospital, Lund, Sweden. lars.edvinsson@med.lu.se
D001812:Blood-Brain Barrier / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D016503:Drug Delivery Systems; D015870:Gene Expression; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide
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