Dihydroergotamine

Medical uses

Subcutaneous and intramuscular injections are generally more effective than the nasal spray and can be self-administered by patients. Intravenous injection is considered very effective for severe migraine or status migrainosus. Dihydroergotamine is also used in the treatment of medication overuse headache.

Dihydroergotamine is indicated for the acute treatment of migraine.

Side effects

Nausea is a common side effect of intravenous administration and less common in other modes. Antiemetics can be given prior to DHE to counteract the nausea. Risks and contraindications are similar to the triptans. DHE and triptans should never be taken within 24 hours of each other due to the potential for coronary artery vasospasm. DHE produces no dependence.

Contraindications

Dihydroergotamine is contraindicated with potent CYP3A4 inhibitors, like macrolide antibiotics.

Contraindications for dihydroergotamine include: pregnancy, kidney failure or liver failure, coronary, cerebral, and peripheral vascular disease, hypersensitivity reactions, sepsis, and uncontrolled hypertension.

Pharmacology

Pharmacodynamics

Dihydroergotamine's antimigraine activity is due to its action as an agonist at the serotonin 5-HT1B, 5-HT1D, and 5-HT1F receptors. It also interacts with other serotonin, adrenergic, and dopamine receptors.

Dihydroergotamine is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy.

In spite of acting as an agonist of the serotonin 5-HT2A receptor, dihydroergotamine has been described as non-hallucinogenic. This is also the case with certain other ergoline derivatives, such as bromocriptine and pergolide.

Pharmacokinetics

Efficacy is variable in the nasal spray form with relative bioavailability of 32% compared to injection.

History

Dihydroergotamine is a semi-synthetic form of ergotamine approved in the US in 1946. Dihydroergotamine is derived from ergot, a fungus that grows on rye and other grains.

Society and culture

Legal status

In 2013, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended that medicines containing ergot derivatives no longer be used to treat several conditions involving problems with memory, sensation or blood circulation, or to prevent migraine headaches because the risks (increased risk of fibrosis and ergotism) were said to be greater than the benefits in these indications.

Brand names

Brand names of dihydroergotamine include Diergo, Dihydergot, D.H.E. 45, Ergont, Ikaran, Migranal, Orstanorm, and Seglor, among others.

References

References

1. Anvisa. (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
2. "D.H.E. 45- dihydroergotamine mesylate injection, solution".
3. "Migranal- dihydroergotamine mesylate spray".
4. "Dromelate- dihydroergotamine mesylate injection, solution".
5. "Trudhesa- dihydroergotamine mesylate spray, metered".
6. (2000). "Index Nominum 2000: International Drug Directory". Taylor & Francis.
7. (April 2005). "Parenteral dihydroergotamine for acute migraine headache: a systematic review of the literature". Annals of Emergency Medicine.
8. (November 2006). "DHE in the pharmacotherapy of migraine: potential for a larger role". Headache.
9. (8 May 2025). "Atzumi- dihydroergotamine mesylate powder".
10. (15 May 2025). "Brekiya- dihydroergotamine mesylate injection".
11. (2024). "StatPearls". StatPearls Publishing.
12. "Dihydroergotamine (DHE) for Migraine Treatment {{!}} AMF".
13. (February 2003). "Ergotamine and dihydroergotamine: a review". Current Pain and Headache Reports.
14. (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". Journal of Pharmacological and Toxicological Methods.
15. National Institute on Drug Abuse. (1994). "NIDA Research Monograph". National Institute on Drug Abuse.
16. (January 2024). "Psychedelics: preclinical insights provide directions for future research". Neuropsychopharmacology.
17. "Ergotamine search results". University of North Carolina Chapel Hill.
18. (February 2003). "Ergotamine and dihydroergotamine: history, pharmacology, and efficacy". Headache.
19. (September 2003). "Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy". British Journal of Pharmacology.
20. (June 1997). "Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy". Naunyn Schmiedebergs Arch Pharmacol.
21. (January 2020). "Dihydroergotamine (DHE) - Then and Now: A Narrative Review". Headache.
22. "Dihydroergotamine (DHE) for Migraine Relief: Are You a Good Candidate? What to Know".
23. (2020). "Updated Evaluation of IV Dihydroergotamine (DHE) for Refractory Migraine: Patient Selection and Special Considerations". Journal of Pain Research.
24. (18 December 2013). "Restrictions on use of medicines containing ergot derivatives".
25. (28 June 2013). "New restrictions on use of medicines containing ergot derivatives".
26. (28 June 2013). "Ergot derivatives".