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CGRP receptor antagonists and antibodies against CGRP and its receptor in migraine treatment.

Edvinsson, Lars LU (2015) In British Journal of Clinical Pharmacology 80(2). p.193-199
Abstract
Recently developed calcitonin gene-related peptide (CGRP) receptor antagonistic molecules have shown promising results in clinical trials for acute treatment of migraine attacks. Drugs from the gepant class of CGRP receptor antagonists are effective and do not cause vasoconstriction, (one of the major limitations in the use of triptans); however their use had to be discontinued because of risk of liver toxicity after continuous exposure. As an alternative approach to block CGRP transmission, fully humanized monoclonal antibodies towards CGRP and the CGRP receptor have been developed for treatment of chronic migraine (attacks >15 days/month). Initial results from phase I and II clinical trials have revealed promising results with minimal... (More)
Recently developed calcitonin gene-related peptide (CGRP) receptor antagonistic molecules have shown promising results in clinical trials for acute treatment of migraine attacks. Drugs from the gepant class of CGRP receptor antagonists are effective and do not cause vasoconstriction, (one of the major limitations in the use of triptans); however their use had to be discontinued because of risk of liver toxicity after continuous exposure. As an alternative approach to block CGRP transmission, fully humanized monoclonal antibodies towards CGRP and the CGRP receptor have been developed for treatment of chronic migraine (attacks >15 days/month). Initial results from phase I and II clinical trials have revealed promising results with minimal side effects and significant relief from chronic migraine as compared to placebo. The effectiveness of these various molecules raises the question of where is the target site(s) for antimigraine action. The gepants are small molecules that can partially pass the blood-brain barrier (BBB) and therefore, might have effects in the CNS. However, antibodies are large molecules and have limited possibility to pass the BBB, thus effectively excluding them from having a major site of action within the CNS. It is suggested that the antimigraine site should reside in areas not limited by the BBB such as intra- and extracranial vessels, dural mast cells, and the trigeminal system. In order to clarify this topic and surrounding questions, it is important to understand the localization of CGRP and the CGRP receptor components in these possible sites of migraine-related regions and their relation to the BBB. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Clinical Pharmacology
volume
80
issue
2
pages
193 - 199
publisher
John Wiley & Sons
external identifiers
  • pmid:25731075
  • wos:000358445700005
  • scopus:84937517146
ISSN
1365-2125
DOI
10.1111/bcp.12618
language
English
LU publication?
yes
id
f3c1335c-f0f1-43b6-82bc-643aa80631f0 (old id 5265544)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25731075?dopt=Abstract
date added to LUP
2015-04-01 17:47:47
date last changed
2017-11-19 03:24:04
@article{f3c1335c-f0f1-43b6-82bc-643aa80631f0,
  abstract     = {Recently developed calcitonin gene-related peptide (CGRP) receptor antagonistic molecules have shown promising results in clinical trials for acute treatment of migraine attacks. Drugs from the gepant class of CGRP receptor antagonists are effective and do not cause vasoconstriction, (one of the major limitations in the use of triptans); however their use had to be discontinued because of risk of liver toxicity after continuous exposure. As an alternative approach to block CGRP transmission, fully humanized monoclonal antibodies towards CGRP and the CGRP receptor have been developed for treatment of chronic migraine (attacks >15 days/month). Initial results from phase I and II clinical trials have revealed promising results with minimal side effects and significant relief from chronic migraine as compared to placebo. The effectiveness of these various molecules raises the question of where is the target site(s) for antimigraine action. The gepants are small molecules that can partially pass the blood-brain barrier (BBB) and therefore, might have effects in the CNS. However, antibodies are large molecules and have limited possibility to pass the BBB, thus effectively excluding them from having a major site of action within the CNS. It is suggested that the antimigraine site should reside in areas not limited by the BBB such as intra- and extracranial vessels, dural mast cells, and the trigeminal system. In order to clarify this topic and surrounding questions, it is important to understand the localization of CGRP and the CGRP receptor components in these possible sites of migraine-related regions and their relation to the BBB.},
  author       = {Edvinsson, Lars},
  issn         = {1365-2125},
  language     = {eng},
  number       = {2},
  pages        = {193--199},
  publisher    = {John Wiley & Sons},
  series       = {British Journal of Clinical Pharmacology},
  title        = {CGRP receptor antagonists and antibodies against CGRP and its receptor in migraine treatment.},
  url          = {http://dx.doi.org/10.1111/bcp.12618},
  volume       = {80},
  year         = {2015},
}