A Support to the Central Link between Serotonin and Acetylcholine in Migraine
  • Maria Nicolodi
  • Federigo Sicuteri
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 467)


Recently synthesized triptans, sumatriptan derivatives, display aborting migraine activity at doses and with plasmatic maximum peak dramatically lower (20-40 times) than sumatriptan, the 5-HT like agonist, which is the original molecule. That triptans easily cross blood-brain barrier strongly supports the central theory of migraine. We recently discovered the anti-migraine prophylactic action of centrally acting anti-cholinesterase agents, that seems a further support to the central theory of migraine. Indeed, acetylcholine is an important analgesia neurotransmitter and is intertwined with 5-HT central pathways.


Cluster Headache Migraine Attack Chronic Migraine Central Theory Migraine Sufferer 
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  1. Bartolini, A., Ghelardini, C., Donaldson, S., Galeotti, N., Nicolodi, M., and Sicuteri, F., 1996, The antimigraine drug ergotamine is endowed with antinociceptive activity. Pharmacol. Res. 35:58.Google Scholar
  2. Fowler, P.A., Lacey, L.F., Thomas, M., Keene, O.N., Tanner, R.J.N., and Baber, N.S., 1991, The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan. Eur. Neurol. 31:291–294.PubMedCrossRefGoogle Scholar
  3. Ghelardini, C., Galeotti, N., Figini, M., Imperato, A., Nicolodi, M., Sicuteri, F., Gessa, G.L., and Bartolini, A., 1996, The central cholinergic system has a role in the antinociception induced in rodents and guinea pigs by the antimigraine drug sumatriptan. J. Pharmacol. Exp. Ther. 279(2):301–306.Google Scholar
  4. Goadsby, P. and Gundlach, A., 1991, Localization of 3H-dihydroergotamine-binding sites in the cat central nervous system: relevance to migraine. Ann. Neurol. 29:91–94.PubMedCrossRefGoogle Scholar
  5. May, A., Gijsman, H.G., Wallnofer, A., Jones, R., Diener, H.C., and Ferrari, M.D., 1996, Endothelin antagonist bosentan blocks neurogenic inflammation, but is not effective in aborting migraine attacks. Pain 67:375–378.PubMedCrossRefGoogle Scholar
  6. Nicolodi, M. and Sicuteri, F., 1993, Visceral heterotopic allodynia and hyperalgesia unmask the hidden dimension of nociceptive disorder in migraine, in: New trends in referred pain and hyperalgesia (L. Vecchiet, D. Albe-Fessard, and U. Lindblom eds.) pp 309–312, Elsevier: Amsterdam.Google Scholar
  7. Nicolodi, M. and Sicuteri, F., 1998, Migraine prophylaxis by brain cholinesterase inhibitors. Int. J. Psychophysiology 30(1:2):27.Google Scholar
  8. Nicolodi, M., 1997, The problem of refractoriness to sumatriptan: does it truly exist? Cephalalgia 16(5):360.Google Scholar
  9. Nicolodi, M., Diadori, A., and Nuti, A., 1997a, Sumatriptan and ergotamine relieve pain argon laser photo-coagulation. Cephalalgia 17:376–377.CrossRefGoogle Scholar
  10. Nicolodi, M., Sicuteri, F., Bartolini, A., Ghelardini, C., and Coppola, G., 1994a, Central actions of sumatriptan in animals and man, in: Advances in headache research (F. Clifford Rose ed.) pp 183–188, Smith-Gordon: London.Google Scholar
  11. Nicolodi, M., Sicuteri, R., Coppola, G., Greco, E., Pietrini, U., and Sicuteri, F., 1994b, Visceral pain threshold is deeply lowered far from the head in migraine. Headache 34 (1):12–19.Google Scholar
  12. Nicolodi, M., Sicuteri, F., Ghelardini, C., Galeotti, N., and Bartolini, A., 1997b, Proposal of an animal model to test specific acute drugs for migraine attacks. Cephalalgia 17:400.CrossRefGoogle Scholar
  13. Pascual, J., Del Arco, C., Ramòn, T, Del Olmo, E., Castro, E., and Pazos, A., 1996, Autoradiographic distribution of (3H) sumatriptan-binding sites in post-mortem human brain. Cephalalgia 16:314–333.CrossRefGoogle Scholar
  14. Raiteri, M., Maura, G., Bonanno, G., Pittaluga, A., Fedele, E., Costa, C., Cerasoli, M.G., and Ulivi, M., 1990, Serotonin receptors regulating transmitter release, in: Serotonin: From Cell Biology to Pharmacology and Therapeutics (R. Paoletti et al., eds.) pp 161–168, Kluwer Academic Publishers: New York.Google Scholar
  15. Seaber, E.O. and Phillips, R., 1996, The tolerability and pharmacokinetics of the novel antimigraine compound 311C90 in healthy male volunteers. British Journal of Clinical Pharmacology 41:141–147.PubMedCrossRefGoogle Scholar
  16. Sicuteri, F., 1959, Prophylactic and therapeutic properties of L-methyl-lysergic acid butanolamide in migraine. Int. Arch. Allergy 15:300–303.PubMedCrossRefGoogle Scholar
  17. Sicuteri, F., 1970, Bradykinin and intracranial circulation in man in: Handbook of experimental pharmacology Vol 25 (Erdös, E.G. ed.) pp 482–495, Springer-Verlag: Berlin.Google Scholar
  18. Sicuteri, F., 1978, Headache as the most common disease of the antinociceptive system: analogies with morphine abstinence, in: Advances in Pain Research and Therapy Vol 3 (J.J. Bonica, J.C. Liebeskind, and D.G. Albe-Fessard, eds.) pp 359–365, Raven Press: New York.Google Scholar
  19. Sicuteri, F., Anselmi, B., and Del Bianco, P.L., 1973, 5-hydroxytryptamine supersensitivity as a new theory of headache and central pain. A clinical pharmacological approach with p-chlorophenylalanine. Psychopharmacology 29:347–356.CrossRefGoogle Scholar
  20. Sicuteri, F., Anselmi, B., and Fanciullacci, M., 1974, The serotonin (5-HT) theory of migraine. Adv. Neurol. 4:383–394.Google Scholar
  21. Sicuteri, F., Del Bene, E., and Anselmi, B., 1976, Fenfluramine headache. Headache 16:185–188.CrossRefGoogle Scholar
  22. Sicuteri, F., Fanciullacci, M., Franchi, G., and Del Bianco, P.L., 1965, Serotonin-bradykinin potentiation on the pain receptors in man. Life Sci. 4:409–410.CrossRefGoogle Scholar
  23. Sicuteri, F., Nicolodi, M., Del Bianco, P.L., and Del Bene, E., 1997, Decentralization monoamine super-sensitivity of migraine and opiate abstinence: common features and different target mechanisms? Int. J. Clin. Pharm. Res. 17(2/3):67–73.Google Scholar
  24. Weiller, C., May, A., Limmroth, V., Juptner, M., Kaube, H., Schayck, R.V., Coenen, H.H., and Diener, H.C., 1995, Brain stem activation in spontaneous human migraine attack. Nature Medicine 1(7):658–669.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Maria Nicolodi
    • 1
  • Federigo Sicuteri
    • 1
  1. 1.Department of Internal Medicine and TherapeuticsInteruniversity Centre of Neurochemistry and Clinical Pharmacology of Idiopathic HeadacheFlorenceItaly

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