Abstract
Primary headaches are among the most prevalent neurological disorders, afflicting up to 16% of the adult population. Associated pain originates from intracranial blood vessels that are innervated by sensory nerves storing several neurotransmitters. In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with other neuronal messengers. The specific purpose of this review is to describe CGRP in the human cranial circulation and to elucidate a possible role for a specific antagonist in the treatment of primary headaches. Acute treatment by administration of a triptan (5-HT1B/1D agonist) results in alleviation of the headache and normalization of the elevated CGRP level. The mechanism of action of triptans involves vasoconstriction of intracranial vessels and a presynaptic inhibitory effect of the trigeminal sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists, which would predictably have less cardiovascular side effects as compared to the triptans. The initial pharmacological profile of such a group of compounds has recently been disclosed. These compounds have high selectivity for human CGRP receptors and are reported to be efficacious in the relief of acute attacks of migraine.
Keywords: Migraine, cluster headache, CGRP, VIP, trigeminovascular reflex, CGRP blockers
CNS & Neurological Disorders - Drug Targets
Title: CGRP-Receptor Antagonism in Migraine Treatment
Volume: 6 Issue: 4
Author(s): Lars Edvinsson and Kenneth Ahrend Petersen
Affiliation:
Keywords: Migraine, cluster headache, CGRP, VIP, trigeminovascular reflex, CGRP blockers
Abstract: Primary headaches are among the most prevalent neurological disorders, afflicting up to 16% of the adult population. Associated pain originates from intracranial blood vessels that are innervated by sensory nerves storing several neurotransmitters. In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with other neuronal messengers. The specific purpose of this review is to describe CGRP in the human cranial circulation and to elucidate a possible role for a specific antagonist in the treatment of primary headaches. Acute treatment by administration of a triptan (5-HT1B/1D agonist) results in alleviation of the headache and normalization of the elevated CGRP level. The mechanism of action of triptans involves vasoconstriction of intracranial vessels and a presynaptic inhibitory effect of the trigeminal sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists, which would predictably have less cardiovascular side effects as compared to the triptans. The initial pharmacological profile of such a group of compounds has recently been disclosed. These compounds have high selectivity for human CGRP receptors and are reported to be efficacious in the relief of acute attacks of migraine.
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Cite this article as:
Lars Edvinsson and Kenneth Ahrend Petersen , CGRP-Receptor Antagonism in Migraine Treatment, CNS & Neurological Disorders - Drug Targets 2007; 6 (4) . https://dx.doi.org/10.2174/187152707781387314
DOI https://dx.doi.org/10.2174/187152707781387314 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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