Title:The locus of Action of CGRPergic Monoclonal Antibodies Against Migraine: Peripheral Over Central Mechanisms
Volume: 19
Issue: 5
Author(s): Abimael González-Hernández, Bruno A. Marichal-Cancino, Enrique García-Boll and Carlos M. Villalón*
Affiliation:
- Departamento de Farmacobiologia, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg, Tlalpan, 14330 Ciudad de Mexico,Mexico
Keywords:
Antibody, antimigraine, CGRP, gepants, headache, pain.
Abstract: Migraine is a complex neurovascular disorder characterized by attacks of moderate to severe
unilateral headache, accompanied by photophobia among other neurological signs. Although an
arsenal of antimigraine agents is currently available in the market, not all patients respond to them. As
Calcitonin Gene-Related Peptide (CGRP) plays a key role in the pathophysiology of migraine, CGRP
receptor antagonists (gepants) have been developed. Unfortunately, further pharmaceutical development
(for olcegepant and telcagepant) was interrupted due to pharmacokinetic issues observed during
the Randomized Clinical Trials (RCT). On this basis, the use of monoclonal antibodies (mAbs; immunoglobulins)
against CGRP or its receptor has recently emerged as a novel pharmacotherapy to treat
migraines. RCT showed that these mAbs are effective against migraines producing fewer adverse
events. Presently, the U.S. Food and Drug Administration approved four mAbs, namely: (i) erenumab;
(ii) fremanezumab; (iii) galcanezumab; and (iv) eptinezumab. In general, specific antimigraine compounds
exert their action in the trigeminovascular system, but the locus of action (peripheral vs. central)
of the mAbs remains elusive. Since these mAbs have a molecular weight of ∼150 kDa, some studies
rule out the relevance of their central actions as they seem unlikely to cross the Blood-Brain Barrier
(BBB). Considering the therapeutic relevance of this new class of antimigraine compounds, the present
review has attempted to summarize and discuss the current evidence on the probable sites of action
of these mAbs.
