Systematic (IUPAC) name
Clinical data
Trade names D.H.E. 45, Migranal
Licence data US FDA:
  • US: X (Contraindicated)
Legal status
Routes of
nasal spray, SC, IM, IV
Pharmacokinetic data
Bioavailability 32% Nasal Spary
Biological half-life 9 hours
Excretion Bile
CAS Registry Number  Y
ATC code N02
PubChem CID:
DrugBank  Y
ChemSpider  Y
Synonyms (5'α)-9,10-dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trione
Chemical data
Formula C33H37N5O5
Molecular mass 583.678 g/mol

Dihydroergotamine ( ; brand names D.H.E. 45 and Migranal) is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. Nausea is a common side effect.[1]

It has similar actions to the triptans, acting as an agonist to the serotonin 5-HT(1D) receptors and causing vasoconstriction of the intracranial blood vessels, but also interacts centrally with dopamine and adrenergic receptors. It can be used to treat acute intractable headache or withdrawal from analgesics.


Dihydroergotamine (DHE) is a semi-synthetic form of ergotamine approved in the US in 1946. Oral bioavailability is poor and it is not available in oral form in the US. DHE is available as Migranal nasal spray and in ampules for subcutaneous, intramuscular and intravenous injection. Efficacy is variable in the nasal spray form with bioavailability 32% of injectable administration. Subcutaneous and intramuscular injections are generally more effective than the nasal spray and can be self-administered by patients.[1] Intravenous injection is considered very effective for severe migraine or status migrainosus. DHE is also used in the treatment of medication overuse headache.[2]
Nausea is a common side effect of IV 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 not be taken within 24 hours of each other due to the potential for coronary artery vasospasm. DHE produces no dependence.[3]
MAP Pharmaceuticals submitted an inhaled version of DHE (Levadex) for FDA approval in May 2011. Allergan acquired the rights to Levadex for nearly $1 billion but approval is still pending from the FDA for its release.

Recently, DHE has been reported to exhibit efficacy in minimising symptoms of orthostatic intolerance in conditions such as the Postural Orthostatic Tachycardia Syndrome. DHE via its selective venous constrictor action may improve stroke volume through enhanced venous return in these patients.

  • European Union

In 2013 the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has 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.[4]


  1. ^ a b Colman, I.; Brown, M. D.; Innes, G. D.; Grafstein, E.; Roberts, T. E.; Rowe, B. H. (2005). "Parenteral Dihydroergotamine for Acute Migraine Headache: A Systematic Review of the Literature". Annals of Emergency Medicine 45 (4): 393–401.  
  2. ^ Saper, J. R.; Silberstein, S.; Dodick, D.; Rapoport, A. (2006). "DHE in the pharmacotherapy of migraine: potential for a larger role". Headache 46 (Suppl 4): S212–S220.  
  3. ^ Schaerlinger, B.; Hickel, P.; Etienne, N.; Guesnier, L.; Maroteaux, L. (2003). "Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy". British Journal of Pharmacology 140 (2): 277–284.  
  4. ^ Restrictions on use of medicines containing ergot derivatives (EMA 2013), Retrieved 3 August 2014

External links

  • DHE prescribing information
  • Migranal prescribing information