Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine

Olesen, Jes; Diener, Hans‐Christoph; Husstedt, Ingo W.; Goadsby, Peter J.; Hall, David B.; Meier, Ulrich; Pollentier, Stephane; Lesko, Lynna M.

doi:10.1056/nejmoa030505

Cited by 1,111 publications

(915 citation statements)

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“…The CGRP receptor antagonist at a dose of 2.5 mg was effective in the treatment of the migraine attack with a response rate of 66% as compared with 27% for placebo. BIBN4096BS also showed significant superiority over placebo in reducing the pain at 2 h and improving the nausea, photophobia, phonophobia, functional capacity and the time to meaningful relief [80]. Side effects were 25% with BIBN4096BS and 12% with placebo.…”

Section: Cgrp Antagonists In Migrainementioning

confidence: 90%

“…A recent clinical trial has shown that BIBN4096BS is effective in the acute treatment of migraine without significant side effects or intrinsic vasoconstrictor effects [80]. The CGRP receptor antagonist at a dose of 2.5 mg was effective in the treatment of the migraine attack with a response rate of 66% as compared with 27% for placebo.…”

Section: Cgrp Antagonists In Migrainementioning

confidence: 99%

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CGRP and migraine: neurogenic inflammation revisited

Geppetti

Capone²,

Trevisani

et al. 2005

J Headache Pain

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The term 'neurogenic inflammation' refers to a series of proinflammatory responses produced by the stimulation of peripheral terminals of a subset of primary sensory neurons and the subsequent release of the neuropeptides, calcitonin gene-related peptide (CGRP) and the tachykinins, substance P (SP) and neurokinin A (NKA) [1]. The neurons that produce inflammation comprise a heterogeneous cell population with A-delta and C fibres, defined as polymodal nociceptors because they sense thermal, chemical and high-threshold mechanical stimuli. These neurons express on their plasma membrane a large panel of excitatory and inhibitory receptors and channels, and some of these signalling proteins have been successfully used as targets for analgesic or anti-inflammatory drugs. Among the channels expressed on peptidergic primary sensory neurons, transient receptor potential vanilloid-1 (TRPV1) [2], activated by the xenobiotic capsaicin, the pungent ingredient of plants of the genus Capsicum, is of paramount importance. Capsaicin produces burning pain by stimulating TRPV1 and by releasing sensory neuropeptides causes neurogenic inflammation. However, high concentrations/doses of capsaicin have the ability, after an initial excitatory phase, to desensitise the sensory nerve terminals, thus reducing the transmission of sensory/pain signals and abolishing neurogenic inflammation [3, 4]. This specific feature of capsaicin has greatly contributed to define the role of this subset of sensory nerves in pathophysiological models of human diseases and has been Pierangelo Geppetti Jay Guido Capone Marcello Trevisani Paola Nicoletti Giovanni Zagli Maria Rosalia Tola Abstract For more than a century neurogenic inflammation has been proposed to have a role in various human diseases. The present review will cover the conceptual steps of the itinerary that has led to the conclusion that neurogenic inflammation is important in migraine. Of particular relevance for the object of this article is the observation that tachykinindependent neurogenic inflammatory responses are evident in rodents, but much less pronounced or absent in other mammal species, including man, whereas neurogenic vasodilatation, most likely mediated by CGRP, occurs in most mammalian species and also in man. Recent evidence that a CGRP receptor antagonist was effective in the treatment of migraine attack supports the hypothesis that neurogenic vasodilatation is a major underlying mechanism of migraine.

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Section: Cgrp Antagonists In Migrainementioning

confidence: 90%

Section: Cgrp Antagonists In Migrainementioning

confidence: 99%

CGRP and migraine: neurogenic inflammation revisited

Geppetti

Capone²,

Trevisani

et al. 2005

J Headache Pain

View full text Add to dashboard Cite

show abstract

“…Recently, CGRP antagonists have been developed with clinical efficacy for the treatment of acute migraine attacks [10-12]. Consequently, it is of considerable importance to clarify where the CGRP receptor is expressed which would indicate possible sites for the therapeutic effect of these antagonists.…”

Section: Introductionmentioning

confidence: 99%

Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

2011

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BackgroundCalcitonin gene-related peptide (CGRP) has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin), synaptophysin (synaptic vesicles) or IB4 (C-fibers in general) were performed.ResultsIn the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy.ConclusionsThis study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1-level, and shows the possibility of CGRP acting postjunctionally in these areas putatively involved in primary headaches.

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“…The affinity of olcegepant for the CGRP receptor was RAMP1 related, directly competing with CGRP for its binding site [73]. In 2004, Olesen et al [74] reported the positive outcomes of CGRP-RA as a migraine-abortive therapy with similar effectiveness to that of oral sumatriptan. A dose of 2.5 mg was considered to be ideal, with a response rate of 66 % as compared with 27 % for placebo (p = 0.001).…”

Section: Cgrp Receptor Antagonistsmentioning

confidence: 99%

Targeting CGRP: A New Era for Migraine Treatment

Goldberg

Silberstein

2015

CNS Drugs

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Migraine is a highly prevalent headache disease that typically affects patients during their most productive years. Despite significant progress in understanding the underlying pathophysiology of this disorder, its treatment so far continues to depend on drugs that, in their majority, were not specifically designed for this purpose. The neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack. It is not surprising that drugs designed to specifically block its action are gaining remarkable attention from researchers in the field with, at least so far, a safe risk profile. In this article, we highlight the evolution from older traditional treatments to the innovative CGRP target drugs that are revolutionizing the way to approach this debilitating neurological disease. We provide a brief introduction on pathophysiology of migraine and details on the characteristic, function, and localization of CGRP to then focus on CGRP receptor antagonists (CGRP-RAs) and CGRP monoclonal antibodies (CGRP mAbs). Key PointsThe neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack.Targeting CGRP as a specific therapeutic tool for migraine may offer similar or even better efficacy than currently available treatments without the vasoconstrictive risk factors.Further studies are necessary to determine the exact role of CGRP receptor antagonists and CGRP monoclonal antibodies in migraine with aura, allodynia, and photophobia.

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Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine

Cited by 1,111 publications

References 32 publications

CGRP and migraine: neurogenic inflammation revisited

CGRP and migraine: neurogenic inflammation revisited

Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

Targeting CGRP: A New Era for Migraine Treatment

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