Endothelin antagonist bosentan blocks neurogenic inflammation, but is not effective in aborting migraine attacks

May, Arne; Gijsman, Harm J.; Wallnöfer, Andreas; Jones, Robert L.; Hc, Diener; Ferrari, Michel D.

doi:10.1016/0304-3959(96)03137-5

Cited by 118 publications

(51 citation statements)

References 9 publications

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“…Redrawn from Saxena and Tfelt-Hansen (2006) trigeminal ganglion or systemic administration of capsaicin, has allowed studies on the activation of the trigeminal system and its effects on the cranial vasculature (for review, see Arulmani et al 2006). This review also contains data on the ability of several drugs to inhibit plasma protein extravasation (e.g., Weiss et al 2006), although it should be kept in mind that extravasation inhibitors, such as CP-122,288 (Roon et al 2000), the neurokinin-1 receptor antagonist lanepitant (Goldstein et al 2001a;Goldstein et al 1997), and the mixed ET A /ET B receptor antagonist bosentan (May et al 1996) proved ineffective in the treatment of migraine. Thus, the relevance of plasma protein extravasation in migraine is no longer tenable (Peroutka 2005).…”

Section: Receptor Subtypes Involved In Pharmacological Treatments Of mentioning

confidence: 99%

“…In rats, ET-1 is one of the most potent inducers of Leão's spreading depression (Dreier et al 2002), but Goadsby et al (1996) reported no effect of endothelin receptor antagonists in preventing spreading depression in cats. The major setback for the hypothesis of involvement of ET-1 in migraine pathogenesis comes from a study showing the lack of efficacy of the mixed ET A /ET B receptor antagonist bosentan in migraine (May et al 1996). However, the ET A and ET B receptors are likely to mediate opposite effects, and it is feasible that more selective endothelin receptor antagonists may be effective in the acute treatment of migraine.…”

Section: Endothelin Receptorsmentioning

confidence: 99%

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Current and prospective pharmacological targets in relation to antimigraine action

Mehrotra

Gupta

Chan

et al. 2008

Naunyn-Schmied Arch Pharmacol

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Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT 1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT 2 receptor antagonists, Ca 2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT 1-7 ), adrenergic (α 1 , α 2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP 2 ), adenosine (A 1 , A 2 , and A 3 ), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon.

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Section: Receptor Subtypes Involved In Pharmacological Treatments Of mentioning

confidence: 99%

Section: Endothelin Receptorsmentioning

confidence: 99%

Current and prospective pharmacological targets in relation to antimigraine action

Mehrotra

Gupta

Chan

et al. 2008

Naunyn-Schmied Arch Pharmacol

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“…Consistent with this, the endothelin receptor antagonist, bosentan, which blocks neurogenic plasma extravasation in the dura mater [Brändli et al, 1996], was ineffective in aborting headache in migraine patients and may be attributable to its lack of vasoconstrictor activity [May et al, 1996]. Endothelins (ET-1 and -3) are potent vasoconstrictors.…”

Section: Cgrp Sp and Nka Involvement In Migrainementioning

confidence: 91%

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

Samsam

Coveñas

Ahangari

et al. 2007

Drug Development Research

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Many factors have been implicated in the pathogenesis of migraine headache, including activation of the trigeminovascular system, dysfunction of: cerebral blood vessels, circulating vasoactive substances, mitochondrial energy metabolism, brain oxygenation and metabolism, platelet disorder, alterations in serotonin levels, low levels of brain tissue magnesium, altered transport of ions across the cell membrane, and inheritance and dysfunction of the brainstem periaqueductal gray matter. The headache phase of migraine is associated with cerebral vasodilation and inflammation, presumably mediated by the release of vasoactive substances and neuropeptides including CGRP (calcitonin gene-related peptide). Increased serum CGRP levels have been detected during migraine and cluster headache. One strategy to treat migraine is to inhibit the release of neuropeptides or to block their receptors. This article briefly reviews some experimental and clinical investigations focused on neuropeptide involvement in migraine. Drug Dev Res 68: 294-314, 2007.

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“…Most of the evidence collected in patients indicates that drugs preventing neurogenic inflammation in animal models fail to be effective in migraine and that substances effective in migraine are relatively ineffective in the model of neurogenic extravasation. In fact, the endothelin antagonist bosentan blocks neurogenic inflammation, but is ineffective in aborting migraine attacks [11]. In addition, two substance P antagonists, RPR100893-201 and lanepitant (a neurokinin-1 antagonist), all potent inhibitors of neurogenic inflammation, were ineffective in acute migraine [12].…”

Section: Neuropeptide Receptor Antagonistsmentioning

confidence: 99%

Seeking the best care for acute migraine

Fanciullacci

2002

J Headache Pain

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In recent years, we have seen exciting advances in the knowledge of mechanisms that underlie migraine. These have thus promoted investigations into new drugs for the management of acute migraine. The major goal in migraine research is to identify and study non-vascular targets for migraine therapy. The 5-HT 1F neuronal receptor is apparently not involved in the vascular effects of triptans. Clinical evaluation of LY33470, a potent agonist of 5-HT 1F receptors, has demonstrated that the drug is effective in ending a migraine attack. These results suggest that 5-HT 1F receptor agonists may represent new antimigraine drugs without cerebrovascular or cardiovascular effects. From the plasma extravasation model of migraine, potential therapeutic targets were identified, although in testing no effects were observed: endothelin and substance P antagonists and the specific serotonin agonist CP 122,288, potent inhibitors of neurogenic inflammation, were ineffective in the treatment of a migraine attack. Since a causative role of CGRP in migraine has been postulated, novel antimigraine drugs include CGRP antagonists. Molecules with highly selective antagonistic action on human CGRP receptors of cerebral circulation have been discovered. These CGRP antagonists are in preclinical and clinical trials and the results are awaited with great interest. In addition, a small pilot study found civamide, a capsaicin derivative which causes CGRP depletion from trigeminal sensory fibers, to be effective in the migraine attack. Both NMDA and non-NMDA receptors for glutamate and related excitatory aminoacids are found on trigeminal neurons; therefore excitatory aminoacid receptor antagonists may provide therapeutic action in migraine. Recently, a glutamate receptor antagonist (LY293558) that had not shown vascular effects in animal models demonstrated an antimigraine effect. More specific compounds are also warranted in confirming nitric oxide inhibition as a therapeutic approach in migraine. Thus, it is likely that in the near future emerging therapies will increasingly meet patients' and physicians' goals.

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Endothelin antagonist bosentan blocks neurogenic inflammation, but is not effective in aborting migraine attacks

Cited by 118 publications

References 9 publications

Current and prospective pharmacological targets in relation to antimigraine action

Current and prospective pharmacological targets in relation to antimigraine action

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

Seeking the best care for acute migraine

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