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Ergotamine and dihydroergotamine: A review

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Abstract

The ergot alkaloids were the first specific antimigraine therapy available. However, with the advent of the triptans, their use in the treatment of migraine has declined and their role has become less clear. This review discusses the pharmacology, efficacy, and safety of the ergots. In randomized clinical trials, oral ergotamine was found to be superior to placebo, but inferior to 100 mg of oral sumatriptan. In contrast, rectal ergotamine was found to have higher efficacy (73% headache relief) than rectal sumatriptan (63% headache relief). Intranasal dihydroergotamine was found to be superior to placebo, but less effective than subcutaneous and intranasal sumatriptan. Ergotamine is still widely used in some countries for the treatment of severe migraine attacks. It is generally regarded as a safe and useful drug if prescribed for infrequent use, in the correct dose, and in the absence of contraindications; however, safer and more effective options do exist in the triptans. In patients with status migrainous and patients with frequent headache recurrence, ergotamine is still probably useful.

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References and Recommended Reading

  1. Tfelt-Hansen P, Saxena PR, Ferrari MD: Ergot alkaloids. In Handbook of Clinical Neurology, vol 21, Intoxications of the nervous system. Part II. Edited by Wolf FA. Amsterdam: Elsevier; 1995:61–78.

    Google Scholar 

  2. Tfelt-Hansen P, Saxena PR: Ergot alkaloids in the acute treatment of migraine. In The Headaches. Edited by Olesen J, Tfelt-Hansen P, Welch KMA. Philadelphia: Lippincott Williams & Wilkins; 2000:399–409. This reference presents an excellent and extensive review of the ergot alkaloids in the acute treatment of migraine.

    Google Scholar 

  3. Graham JR, Wolff HG: Mechanism of migraine headache and action of ergotamine tartrate. Arch Neurol Psychiatr 1938, 39:737–763.

    CAS  Google Scholar 

  4. Buzzi MG, Moskowitz MA: Evidence for 5-HT1B/1D receptors mediating the antimigraine effect of sumatriptan and dihydroergotamine. PMID 1991, 11:165–168.

    CAS  Google Scholar 

  5. Buzzi MG, Moskowitz MA, Peroutka SJ, Byun B: Further characterization of the putative 5HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater. Br J Pharmacol 1991, 103:1421–1428.

    PubMed  CAS  Google Scholar 

  6. Hoskin KL, Kaube H, Goadsby PG: Central activation of the trigeminovascular pathway in the cat is inhibited by dihydroergotamine: a c-Fos and electrophysiologic study. Brain 1996, 119:249–256.

    Article  PubMed  Google Scholar 

  7. Tfelt-Hansen P: Ergotamine, dihydroergotamine: current uses and problems. Curr Med Res Opin 2001, 17(suppl 1):30–34. A recent review with the personal point of view of the author regarding the current uses and problems of ergotamine and dihydroergotamine.

    Article  Google Scholar 

  8. Iversen HK, Nielsen TH, Olesen J, Tfelt-Hansen P: Arterial responses during migraine headaches. Lancet 1990, 336:837–839.

    Article  PubMed  CAS  Google Scholar 

  9. Stoll A: Zur Zenntinis der Mutterkornakkaloide. Verh Naturf Ges (Basel) 1920, 101:190–191.

    Google Scholar 

  10. Silberstein SD: The pharmacology of ergotamine and dihydroergotamine. Headache 1997, 37(suppl):15–25.

    PubMed  Google Scholar 

  11. Stevens AA: Modern Materia Medica and Therapeutics. Philadelphia: WB Saunders; 1907.

    Google Scholar 

  12. MüIler-Schweinitzer E: Pharmacologic actions of the main metabolites of dihydroergotamine. Eur J Clin Pharmacol 1984, 26:699–705.

    Article  Google Scholar 

  13. Müller-Schweinitzer E. Weidmann H: Basic pharmacologic properties. In Ergot Alkaloids and Related Compounds. Edited by Berde B, Schild HO. Berlin: Springer-Verlag; 1978:87–232.

    Google Scholar 

  14. Welch KM, D’Andrea G, Tepley N, et al.: The concept of migraine as a state of central neuronal hyperexcitability. Neurol Clin 1990, 8:817–828.

    PubMed  CAS  Google Scholar 

  15. Welch KM, Barkley GL, Tepley N, et al.: Central neurogenic mechanisms of migraine. Neurology 1993, 43:S21-S25.

    PubMed  CAS  Google Scholar 

  16. Lauritzen M: Pathophysiology of the migraine aura: the spreading depression theory. Brain 1994, 117:199–210.

    Article  PubMed  Google Scholar 

  17. Lance JW, Lambert GA, Goadsby PJ, Duckworth JW: Brainstem influences on the cephalic circulation: experimental data from cat and monkey of relevance to the mechanism of migraine. Headache 1983, 23:258–265.

    Article  PubMed  CAS  Google Scholar 

  18. Welch KM, Nagesh V, Aurora SK, Gelman N: Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Headache 2001, 41:629–637.

    Article  PubMed  CAS  Google Scholar 

  19. Saito K, Markowitz S, Moskowitz MA: Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches. Ann Neurol 1988, 24:732–737.

    Article  PubMed  CAS  Google Scholar 

  20. Goadsby PJ, Gundlach AL: Localization c: 3H-dihydroergotamine-binding sties in the cat central nervous system: relevance to migraine. Ann Neurol 1991, 29:91–94.

    Article  PubMed  CAS  Google Scholar 

  21. Tfelt-Hansen P, Eickhoff JH, Olesen J: The effect of single dose ergotamine tartrate on peripheral arteries in migraine patients: methodological aspects and time effect curve. Acta Pharmacol Toxicol 1980, 47:151–156.

    Article  CAS  Google Scholar 

  22. Tfelt-Hansen P: Clinical pharmacology of ergotamine: an overview. In Drug-Induced Headache. Edited by Diener HC, Wilkinson M. Berlin: Springer-Verlags; 1988:105–116.

    Google Scholar 

  23. Perrin VL: Clinical pharmacokinetics of ergotamine in migraine and cluster headache. Clin Pharmacokinet. 1985, 10:334–352.

    Article  PubMed  CAS  Google Scholar 

  24. Buzzi MG, Moskowitz MA, Peroutka SJ, Byun B: Further characterization of the putative 5-HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater. Br J Pharmacol 1991, 103:1421–1428.

    PubMed  CAS  Google Scholar 

  25. Little PJ, Jennings GL, Skews H, et al.: Bioavailability of dihydroergotamine in man. Br J Clin Pharmacol 1982, 13:785–790.

    PubMed  CAS  Google Scholar 

  26. Sandoz Pharmaceuticals Corporation: East Hanover, NJ. Data on file.

  27. Ziegler D, Ford R, Kriegler J, et al.: Dihydroergotamine nasal spray for the acute treatment of migraine. Neurology 1994, 44:447–453.

    PubMed  CAS  Google Scholar 

  28. Mathew NT: The abortive treatment of migraine. In Drug Therapy for Headache. Edited by Gallagher RM. New York: Marcel Dekker; 1991:95–114.

    Google Scholar 

  29. Saper JR, Silberstein SD, Gordon CD, Hamel RL: Medications used in the pharmacotherapy of headache. In Handbook of Headache Management: A Practical Guide to Diagnosis and Treatment of Head, Neck, and Facial Pain. Edited by Silberstein SD, Lipton RB. Baltimore: Williams & Wilkins; 1993:35–47.

    Google Scholar 

  30. Mathew NT: Dosing and administration of ergotamine tartrate and dihydroergotamine. Headache 1997, (suppl 1):26–32.

  31. Baumel B: Migraine: a pharmacologic review with newer options and delivery modalities. Neurology 1994, 44(suppl 3):S13-S17.

    PubMed  CAS  Google Scholar 

  32. Silberstein SD, Young WB: Safety and efficacy of ergotamine tartrate and dihydroergotamine in the treatment of migraine and status migrainous. Neurology 1995, 45:577–584.

    PubMed  CAS  Google Scholar 

  33. Berde B, Stürmer E: Introduction to the pharmacology of ergot alkaloids and related compounds as a basis of their therapeutic application. In Ergot Alkaloids and Related Compounds. Edited by Berde B, Schild HO. Berlin: Springer-Verlag; 1978:1–28.

    Google Scholar 

  34. Chu D, Owen DAA, Stürmer E: Effects of ergotamine and dihydroergotamine on the resistance and capacitance vessels of skin and skeletal muscle in the cat. Postgrad Med J 1976, 52(suppl 1):32–36.

    CAS  Google Scholar 

  35. Winner P, Dalessio D, Mathew N, et al.: Office-based treatment of acute migraine with dihydroergotamine mesylate. Headache 1993, 33:471–475.

    Article  PubMed  CAS  Google Scholar 

  36. Winner P, Ricalde O, LeForce B, et al.: A double-blind study of subcutaneous dihydroergotamine versus subcutaneous sumatriptan in the treatment of acute migraine. Acta Neurol 1996, 53:180–184.

    CAS  Google Scholar 

  37. Belgrade MJ, Ling LJ, Schleevogt MB, et al.: Comparison of single-dose meperidine, butorphanol, and dihydroergotamine in the treatment of vascular headache. Neurology 1989, 39:590–592.

    PubMed  CAS  Google Scholar 

  38. Weisz MA, El-Raheb M, Blumenthal HJ: Home administration of intramuscular DHE for the treatment of acute migraine headache. Headache 1994, 34:371–373.

    Article  PubMed  CAS  Google Scholar 

  39. Ziegler D, Ford R, Kriegler J, et al.: Dihydroergotamine nasal spray for the acute treatment of migraine. Neurology 1994, 44:447–453.

    PubMed  CAS  Google Scholar 

  40. Mather PJ, Silberstein SD, Schulman EA, Hopkins MM: The treatment of cluster headache with repetitive IV dihydroergotamine. Headache 1991, 31:525–532.

    Article  PubMed  CAS  Google Scholar 

  41. Raskin NH: Modern pharmacotherapy of migraine. Neurol Clin 1990, 8:857–865.

    PubMed  CAS  Google Scholar 

  42. Silberstein SD, Schulman EA, Hopkins MM: Repetitive IV DHE in the treatment of refractory headache. Headache 1990, 30:334–339.

    Article  PubMed  CAS  Google Scholar 

  43. Winner P, Dalessio D, Mathew N, et al.: Concomitant administration of antiemetics is not necessary with intramuscular dihydroergotamine. Am J Emerg Med 1994, 12:138–141.

    Article  PubMed  CAS  Google Scholar 

  44. Tfelt-Hansen P, Saxena PR, Dahlof C, et al.: Ergotamine in the acute treatment of migraine: European Consensus. Brain 2000, 123:9–18. Presents the European Consensus regarding the treatment of migraine with ergotamine.

    Article  PubMed  Google Scholar 

  45. Swedish Medical Products Agency: Monograph on sumatriptan suppositories. Accessible at http://mpa.se/lakemedel/ nn_lakeindex.html. Accessed July 5, 2001.

  46. Callaham M, Raskin N: A controlled study of dihydroergotamine in the treatment of acute migraine headache. Headache 1986, 26:168–171.

    Article  PubMed  CAS  Google Scholar 

  47. Scott AK: Dihydroergotamine: a review of its use in the treatment of migraine and other headaches. Clin Neuropharmacol 1992, 15:289–292.

    Article  PubMed  CAS  Google Scholar 

  48. Gallagher RM: Dihydroergotamine working group: acute treatment of migraine with dihydroergotamine nasal spray. Arch Neurol 1996, 53:1285–1291.

    PubMed  CAS  Google Scholar 

  49. Queiroz LP, Weeks RE, Rapoport AM, et al.: Early and transient side effects of repetitive IV dihydroergotamine. Headache 1996, 36:291–294.

    Article  PubMed  CAS  Google Scholar 

  50. Galer BS, Lipton RB, Solomon S, et al.: Myocardial ischemia related to ergot alkaloids: a case report and literature review. Headache 1991, 31:446–450.

    Article  PubMed  CAS  Google Scholar 

  51. Scott AK: Dihydroergotamine: a review of its use in the treatment of migraine and other headaches. Clin Neuropharmacol 1992, 15:289–296.

    Article  PubMed  CAS  Google Scholar 

  52. Maassen Van Den Brink A, Reekers M, Bax WA, et al.: Coronary side-effect potential of current and prospective antimigraine drugs. Circulation 1998, 7:25–30.

    Google Scholar 

  53. Lipton RB: Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache 1997, 37(suppl 1):33–41.

    Google Scholar 

  54. Physicians’ Desk Reference, edn 49: Medical Economics Data. Montvale, NJ; 1995:1840,2149,2153.

  55. Welch KMA: Relationship of stroke and migraine. Neurology 1994, 44(suppl 7):S33-S36.

    PubMed  CAS  Google Scholar 

  56. Meyler WJ: Side effects of ergotamine. Cephalalgia 1996, 16:5–10.

    Article  PubMed  CAS  Google Scholar 

  57. Saper J: Ergotamine dependency: a review. Headache 1987, 27:435–438.

    Article  PubMed  CAS  Google Scholar 

  58. Silberstein SD, Saper JR, Freitag FG: Migraine, diagnosis, and treatment. In Wolff’s Headache and Other Head Pain. Edited by Silberstein SD, Lipton RB, Dalession DJ. New York: Oxford; 2001:121–237.

    Google Scholar 

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Bigal, M.E., Tepper, S.J. Ergotamine and dihydroergotamine: A review. Current Science Inc 7, 55–62 (2003). https://doi.org/10.1007/s11916-003-0011-7

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