The locus of Action of CGRPergic Monoclonal Antibodies Against Migraine: Peripheral Over Central Mechanisms
Por:
Gonzalez-Hernandez, Abimael, Marichal-Cancino, Bruno A., Garcia-Boll, Enrique, Villalon, Carlos M.
Publicada:
1 ene 2020
Resumen:
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 pharmacolcinetic
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 similar to 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.
Filiaciones:
Gonzalez-Hernandez, Abimael:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Blvd Juriquilla 3001, Queretaro 76230, Mexico
Marichal-Cancino, Bruno A.:
Univ Autonoma Aguascalientes, Dept Fisiol & Farmacol, Ciudad Univ, Aguascalientes 20131, Aguascalientes, Mexico
Garcia-Boll, Enrique:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Blvd Juriquilla 3001, Queretaro 76230, Mexico
Villalon, Carlos M.:
Cinvestav Coapa, Dept Farmacobiol, Czda Tenorios 235, Ciudad De Mexico 14330, Mexico
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