European Journal of Clinical Pharmacology

, Volume 30, Issue 5, pp 581–584

Venoconstrictor effects of dihydroergotamine after intranasal and intramuscular administration

  • W. H. Aellig
  • J. Rosenthaler
Originals

Summary

A parenteral formulation of dihydroergotamine (DHE) is the only galenical form now available for the treatment of acute attacks of migraine in which a rapid onset of action is required. A recently developed nasal spray of DHE has been compared with intramuscular DHE for its venoconstrictor activity. In a randomised double-blind, cross-over trial, 9 healthy male volunteers received a single dose of DHE 1 mg intranasally, DHE 0.5 mg i.m. or placebo (intranasally and i.m.) on three different occasions, with an interval of at least 1 week between doses. Both active treatments, but not placebo, produced marked venoconstriction as shown by reduced compliance of superficial hand veins. The effect persisted for more than 8 h. The maximum venoconstrictor effect of 1 mg DHE intransally was 40±12% (mean ± SEM) and after 0.5 mg i.m. it was 52±15%. The time course of the venoconstrictor effect was similar after both routes of administration. Blood pressure and heart rate changes in these normotensive subjects were almost identical after dihydroergotamine and placebo. The results suggest that the nasal spray could be used as an alternative to parenteral DHE, permitting self-administration of the drug for the treatment of acute attacks of migraine.

Key words

dihydroergotamine venoconstriction nasal spray healthy volunteers i.m. administration 

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References

  1. Aellig WH (1974) Venoconstrictor effect of dihydroergotamine in superficial hand veins. Eur J Clin Pharmacol 7: 137–139Google Scholar
  2. Aellig WH (1981) A new technique for recording compliance of human hand veins. Br J Clin Pharmacol 11: 237–243Google Scholar
  3. Aellig WH (1984) Investigation of the venoconstrictor effect of 8'hydroxydihydroergotamine, the main metabolite of dihydroergotamine in man. Eur J Clin Pharmacol 26: 239–242Google Scholar
  4. Aellig WH (1985) Direct effects of vasoactive substances on superficial human veins in vivo. Inter Angio 4: 235–242Google Scholar
  5. Bousser MG, Loria Y (1985) Efficacy of dihydroergotamine nasal spray in the acute treatment of migraine attacks. Cephalalgia 5 [Suppl 3]: 554–555Google Scholar
  6. Brooke OG, Robinson BF (1970) Effect of ergotamine and ergometrine on forearm venous compliance in man. Br Med J 1: 139–142Google Scholar
  7. Kiechel JR (1984) The bioavailability and kinetics of dihydroergotamine. In: P. Fitscha (ed) Neuester Stand der Dihydergot-Forschung. Georg Thieme, Stuttgart New York, pp 32–46Google Scholar
  8. Krause KH, Bleicher MA (1985) Dihydroergotamine nasal spray in the treatment of migraine attacks. Cephalalgia 5 [Suppl 3]: 138–139Google Scholar
  9. Mellander S, Nordenfelt I (1970) Comparative effects of dihydroergotamine and noradrenaline on resistance, exchange and capacitance functions in the peripheral circulation. Clin Sci 39: 183–201Google Scholar
  10. Paalzow LK, Tfelt-Hansen P (1983) Biologisk tillgänglighet och farmakologisk effect av ergotamin. Läkartidningen 19: 2019–2020Google Scholar
  11. Rosenthaler J, Munzer H, Voges R, Andres H, Gull P, Bolliger G (1984) Immunoassay of ergotamine and dihydroergotamine using a common 3H-labelled ligand as tracer for specific antibody and means to overcome experienced pitfalls. Int J Nucl Med Biol 11: 85–89Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • W. H. Aellig
    • 1
  • J. Rosenthaler
    • 2
  1. 1.Cardiovascular DepartmentClinical ResearchBaselSwitzerland
  2. 2.Biopharmaceutical Department, Pharmaceutical DevelopmentSandoz Ltd.BaselSwitzerland

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