Calcitonin gene-related peptide and its role in migraine pathophysiology - PubMed (original) (raw)
Review
Calcitonin gene-related peptide and its role in migraine pathophysiology
Udayasankar Arulmani et al. Eur J Pharmacol. 2004.
Abstract
Migraine is a common neurological disorder that is associated with an increase in plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a neuropeptide released from activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Therefore, it is propounded that: (i) CGRP may have an important role in migraine pathophysiology, and (ii) inhibition of trigeminal CGRP release or CGRP-induced cranial vasodilatation may abort migraine. In this regard, triptans ameliorate migraine headache primarily by constricting the dilated cranial blood vessels and by inhibiting the trigeminal CGRP release. In order to explore the potential role of CGRP in migraine pathophysiology, the advent of a selective CGRP receptor antagonist was obligatory. The introduction of di-peptide CGRP receptor antagonists, namely BIBN4096BS (1-piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl] amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [R-(R*,S*)]-), is a breakthrough in CGRP receptor pharmacology and can be used as a tool to investigate the role of CGRP in migraine headaches. Preclinical investigations in established migraine models that are predictive of antimigraine activity have shown that BIBN4096BS is a potent CGRP receptor antagonist and that it has antimigraine potential. Indeed, a recently published clinical study has reported that BIBN409BS is effective in treating acute migraine attacks without significant side effects. The present review will discuss mainly the potential role of CGRP in the pathophysiology of migraine and the various treatment modalities that are currently available to target this neuropeptide.
Similar articles
- Effects of the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS on alpha-CGRP-induced regional haemodynamic changes in anaesthetised rats.
Arulmani U, Schuijt MP, Heiligers JP, Willems EW, Villalón CM, Saxena PR. Arulmani U, et al. Basic Clin Pharmacol Toxicol. 2004 Jun;94(6):291-7. doi: 10.1111/j.1742-7843.2004.pto940606.x. Basic Clin Pharmacol Toxicol. 2004. PMID: 15228501 - The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs.
Villalón CM, Olesen J. Villalón CM, et al. Pharmacol Ther. 2009 Dec;124(3):309-23. doi: 10.1016/j.pharmthera.2009.09.003. Epub 2009 Sep 29. Pharmacol Ther. 2009. PMID: 19796656 Review. - [CGRP antagonists: novel concept for treatment of migraine].
Nieber K. Nieber K. Med Monatsschr Pharm. 2009 May;32(5):182-5. Med Monatsschr Pharm. 2009. PMID: 19469188 Review. German. - Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine.
Messlinger K, Fischer MJ, Lennerz JK. Messlinger K, et al. Keio J Med. 2011;60(3):82-9. doi: 10.2302/kjm.60.82. Keio J Med. 2011. PMID: 21979827 Review.
Cited by
- Real-World Evidence of the Safety and Effectiveness of Atogepant Added to OnabotulinumtoxinA for the Preventive Treatment of Chronic Migraine: A Retrospective Chart Review.
Blumenfeld AM, Mechtler L, Cook L, Rhyne C, Jenkins B, Hughes O, Dabruzzo B, Manack Adams A, Diamond M. Blumenfeld AM, et al. Pain Ther. 2024 Sep 17. doi: 10.1007/s40122-024-00649-8. Online ahead of print. Pain Ther. 2024. PMID: 39287781 - The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats.
Vogler B, Kuhn A, Mackenzie KD, Stratton J, Dux M, Messlinger K. Vogler B, et al. Int J Mol Sci. 2023 Aug 30;24(17):13471. doi: 10.3390/ijms241713471. Int J Mol Sci. 2023. PMID: 37686275 Free PMC article. - Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine.
Scuteri D, Tonin P, Nicotera P, Vulnera M, Altieri GC, Tarsitano A, Bagetta G, Corasaniti MT. Scuteri D, et al. Toxins (Basel). 2022 Aug 1;14(8):529. doi: 10.3390/toxins14080529. Toxins (Basel). 2022. PMID: 36006191 Free PMC article. - [CGRP antibodies in migraine prophylaxis : The new standard in migraine treatment?].
Hamann T, Rimmele F, Jürgens TP. Hamann T, et al. Schmerz. 2022 Feb;36(1):59-72. doi: 10.1007/s00482-021-00613-x. Epub 2022 Jan 18. Schmerz. 2022. PMID: 35041064 German. - α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine.
Gray ALH, Antevska A, Link BA, Bogin B, Burke SJ, Dupuy SD, Collier JJ, Levine ZA, Karlstad MD, Do TD. Gray ALH, et al. Chem Sci. 2021 Mar 24;12(16):5853-5864. doi: 10.1039/d1sc01167g. Chem Sci. 2021. PMID: 34168810 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials