Journal article
New insights into the molecular actions of serotonergic antimigraine drugs
Pharmacology & therapeutics (Oxford), Vol.94(1), pp.77-92
2002
DOI: 10.1016/S0163-7258(02)00173-0
PMID: 12191595
Abstract
Migraine is a painful and debilitating neurological disorder that affects ∼10% of the adult population in Western countries. Sensitization and activation of the trigeminal ganglia nerves that innervate the meningeal blood vessels is believed to play an important role in the initiation and maintenance of migraine pain. In this capacity, release of the neuropeptide calcitonin gene-related peptide (CGRP) and the resultant neurogenic inflammation is thought to underlie the pathophysiology of migraine. Largely due to the success of the serotonin Type 1 migraine drugs such as sumatriptan, migraine pathology and therapy has become a focus of intensive clinical and physiological research during the past decade. The effectiveness of these drugs is thought to be due to their ability to block the stimulated secretion of neuropeptides from trigeminal nerves to break the vicious nociceptive cycle of migraine. A component of this nociceptive cycle involves activation of mitogen-activated protein kinase signaling pathways. Indeed, activation of mitogen-activated protein kinase pathways can increase CGRP neuropeptide synthesis and secretion. Recently, the serotonin Type 1 agonists have been shown to cause a prolonged increase in intracellular Ca
2+ in trigeminal ganglia neurons and an increased phosphatase activity that can repress stimulated CGRP secretion and transcription. Identification of molecular signaling events in migraine pathology and therapy has provided new insight into the pharmacology and signaling mechanisms of sumatriptan and related drugs, and may provide the foundation for development of novel treatments for migraine.
Details
- Title: Subtitle
- New insights into the molecular actions of serotonergic antimigraine drugs
- Creators
- Paul L Durham - Department of Biology, 225 Temple Hall, Southwest Missouri State University, Springfield, MO 65804, USAAndrew F Russo - Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Pharmacology & therapeutics (Oxford), Vol.94(1), pp.77-92
- DOI
- 10.1016/S0163-7258(02)00173-0
- PMID
- 12191595
- NLM abbreviation
- Pharmacol Ther
- ISSN
- 0163-7258
- eISSN
- 1879-016X
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100003983, name: National Headache Foundation; DOI: 10.13039/100012489, name: Boston Area Diabetes Endocrinology Research Center, award: DK-25295; DOI: 10.13039/100000002, name: National Institutes of Health, award: HD-25969, HL-14388, NS-37386
- Language
- English
- Date published
- 2002
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020629002771
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