Summary
Sumatriptan is a selective agonist for a 5-HT1 -like receptor sub-type which mediates contraction of some cranial blood vessels in vitro. It has been shown to be a very effective novel agent for the acute treatment of migraine and this has stimulated much interest in its clinical mode of action. It has been suggested that the pain of migraine results from a sterile neurogenic inflammatory response of intracranial blood vessels innervated by the trigeminal nerve. Furthermore, sumatriptan has been shown to inhibit plasma protein extravasation from blood vessels of the dura mater, induced by antidromic stimulation of the trigeminal nerve in the anaesthetised rat and guinea-pig. This effect could be explained by a localised vasoconstriction of the meningeal vessels. We now provide evidence that sumatriptan will potently constrict the blood vessels within the human isolated perfused dura mater. Preliminary work on characterising the 5-HT receptor involved indicates that it is a 5-HT1- like receptor. These studies add weight to the view that the anti-migraine action of sumatriptan results from selective cranial vasoconstriction.
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References
Blau, J. N. (1978). Migraine: A vasomotor instability of the meningeal circulation. Lancet 1136–1139.
Bradley, P. B., Engel, G., Feniuk, W., Fozard, J. R., Humphrey, P. P. A., Middlemiss, D. N., Mylecharane, E. J., Richardson, B. P., and Saxena, P. R. (1986). Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25: 563–576.
Buzzi, M. G., and Moskowitz, M. A. (1990). The anti-migraine drug sumatriptan (GR43175) selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br. J. Pharmacol. 99: 202–206.
Connor, H. E., Feniuk, W., and Humphrey, P. P. A. (1989). Characterization of 5-HT receptors mediating contraction of canine and primate basilar artery by use of GR43175, a selective 5-HT1-like receptor agonist. Br. J. Pharmacol. 96: 379–387.
Den Boer, M. O., Villaón, C. M., Heiligers, J. P. C., Humphrey, P. P. A., and Saxena, P. R. (1991). The role of 5-HT1-like receptors in the reduction of porcine arteriovenous shunting by sumatriptan. Br. J. Pharmacol. 102: 323–330.
Feniuk, W., Humphrey, P. P. A., Perren, M. J., and Watts, A. D. (1985). A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. Br. J. Pharmacol. 86: 697–704.
Feniuk, W., Humphrey, P. P. A., and Perren, M. J. (1989). The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetized dogs. Br. J. Pharmacol. 96: 83–90.
Feniuk, W., Humphrey, P. P. A., Perren, M. J., Connor, H. E., and Whalley, E. T. (1990). The rationale for the use of sumatriptan in the treatment of migraine. J. Neurology. 238: S57 - S61.
Graham, J. R., and Wolff, H. G. (1938). Mechanism of migraine headache and action of ergotamine tartrate. Arch. Neurol. Psychiat. Chicago 39: 737–763.
Humphrey, P. P. A. (1990). 5-Hydroxytryptamine and the pathophysiology of migraine. J. Neurology. 238: S38 - S44.
Humphrey, P. P. A., Feniuk, W., Perren, M. J., Connor, H. E., Oxford, A. W., Coates, I. H., and Butina, D. (1988). GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br. J. Pharmacol. 94: 1123–1132.
Humphrey, P. P. A., Feniuk, W., Perren, M. J., Oxford, A. W., and Brittain, R. T. (1989a). Sumatriptan succinate. Drugs of the Future 14 (1): 35–39.
Humphrey, P. P. A., Feniuk, W., Perren, M. J., Connor, H. E., and Oxford, A. W. (1989b). The pharmacology of the novel 5-HT1-like receptor agonist, GR43175. Cephalalgia 9 (Suppl. 9): 23–33.
Humphrey, P. P. A., Apperley, E., Feniuk, W., and Perren, M. J. (1990a). A rational approach to identifying a fundamentally new drug for the treatment of migraine. In Saxena, P. R., Wallis, D. 1., Wouters, W., and Bevan, P. (eds.), Cardiovascular pharmacology of 5-hydroxytryptamine Dordrecht: Kluwer, pp. 417–431.
Humphrey, P. P. A., Feniuk, W., Perren, M. J., Beresford, I. J. M., Skingle, M., and Whalley, E. T. (1990b). Serotonin and migraine. Annals of New York Academy of Sciences. 600: 587–598.
Lance, J. W. (1973). The mechanism and management of headache. Second edition, London: Butterworths.
Moskowitz, M. A. (1984). Neurobiology of vascular head pain. Annals of Neurology 16: 157–168.
Moskowitz, M. A., and Buzzi, M. G. (1991). Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions. J. Neurology. 238: S18 - S22.
Nichols, F. T., Mawad, M., Mohr, J. P., Stein, B., Hilal, S., and Michelsen, W. J. (1990). Focal headache during balloon inflation in the internal carotid and middle cerebral arteries. Stroke 21: 555–559.
Parsons, A. A., Whalley, E. T., Feniuk, W., Connor, H. E., and Humphrey, P. P. A. (1989). 5-HT,-like receptors mediate 5-hydroxytryptamine-induced contraction of human isolated basilar artery. Br. J. Pharmacol. 96: 434–449.
Perren, M. J., Feniuk, W., and Humphrey, P. P. A. (1989). The selective closure of feline carotid arteriovenous anastomoses (AVAs) by GR43175. Cephalalgia 9 (Supp1.9): 41–46.
Saxena, P. R., and Ferrari, M. D. (1989). 5-HT1-like receptor agonists and the pathophysiology of migraine. Trends Pharmacol. Sci. 10: 200–204.
Sleight, A. J., Cervenka, A., and Peroutka, S. J. (1990). In vivo effects of sumatriptan (GR43175) on extracellular levels of 5-HT in the guinea pig. Neuropharmacology 29: 511–513.
Williams, T. J., and Peck, M. J. (1977). Role of prostaglandin-mediated vasodilatation in inflammation. Nature 270: 530–532.
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© 1991 Birkhäuser Verlag Basel/Switzerland
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Humphrey, P.P.A., Feniuk, W., Motevalian, M., Parsons, A.A., Whalley, E.T. (1991). The Vasoconstrictor Action of Sumatriptan on Human Isolated Dura Mater. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_42
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DOI: https://doi.org/10.1007/978-3-0348-7259-1_42
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