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Pronunciation/dˌhdr.ɜːrˈɡɒtəmn/ dy-HY-droh-ur-GOT-ə-meen
Trade namesD.H.E. 45, Migranal, others
Other namesDHE; (5'α)-9,10-Dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trione
  • (2R,4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[,6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[,7.012,16]hexadeca-1(16),9,12,14-tetraene-4-carboxamide
Clinical data
Main usesMigraines, cluster headaches[1]
Side effectsHigh blood pressure, flushing, myocardial ischemia, stroke, ergotism[1]
InteractionsCYP3A4 inhibitors[1]
BreastfeedingNot recommended[2]
Routes of
Nasal spray, SC, IM, IV[3]
Onset of actionWithin 5 min (IV), About 30 min (IN)[1]
External links
License data
Legal status
Bioavailability32% (nasal spray)
Elimination half-life9 hours
Chemical and physical data
Molar mass583.689 g·mol−1
3D model (JSmol)
  • [H][C@]56C[C@@H](C(=O)N[C@]1(C)O[C@]4(O)N(C1=O)[C@@H](Cc2ccccc2)C(=O)N3CCC[C@]34[H])CN(C)[C@]5([H])Cc7c[nH]c8cccc6c78
  • InChI=1S/C33H37N5O5/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32/h3-6,8-11,17,21,23,25-27,34,42H,7,12-16,18H2,1-2H3,(H,35,39)/t21-,23-,25-,26+,27+,32-,33+/m1/s1 checkY

Dihydroergotamine (DHE), sold under the brand name Migranal among others, is a medication used to treat migraines, cluster headaches, and medication overuse headaches.[1][2] It has a particular benefit in hard to treat migraines.[4] It may be used as a nasal spray or by injection.[3] Onset is within 5 to 30 minutes.[1]

Common side effects include high blood pressure, flushing, sweating, and nausea.[1] Other side effects may include myocardial ischemia, stroke, arrhythmia, and ergotism.[1] Use is not recommended during pregnancy, in those with liver or kidney problems, or those with vascular disease.[3] It is a derivative of ergotamine.[4] It activates serotonin receptors as well as dopamine and adrenergic receptors.[4]

Dihydroergotamine was first made in 1943 and has been in medical use since.[3][4] It is available as a generic medication.[5] In the United States it costs about 45 USD per dose by injection and 370 USD per dose in the nose as of 2021.[5][6] As of the 2010s it is less commonly used than triptans.[7]

Medical uses

Subcutaneous and intramuscular injections are generally more effective than the nasal spray and can be self-administered.[8] Intravenous injection is considered very effective for severe migraine or status migrainosus.[2] DHE is also used in the treatment of medication overuse headache.[9]


It may be used as a 1 mg intravenous or intramuscular dose, with this repeated after 1 hour if not effective.[1]

When used in the nose a 0.5 mg spray is given in each nostril, which may be repeated in 15 minutes if needed.[1]

Side effects

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 never be taken within 24 hours of each other due to the potential for coronary artery vasospasm. DHE produces no dependence.[10]



DHE'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.[11]

DHE is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy.[12]

Activities of dihydroergotamine at various sites[13][14][10]
Site Affinity (Ki/IC50 [nM]) Efficacy (Emax [%]) Action
5-HT1A 0.4–1.5 ? Agonist
5-HT1B 0.006–18 ? Agonist
5-HT1D 0.13–0.5 ? Agonist
5-HT1E 1,100 ? ?
5-HT1F 180 ? Agonist
5-HT2A 9.0 ? Agonist
5-HT2B 15–33 ? Agonist
5-HT2C 1.3 ? Agonist
5-HT3 >3,700–>10,000 ? ?
5-HT4 60 ? ?
5-HT5A ? ? ?
5-HT5B ? ?
5-HT6 5.4 ? ?
5-HT7 9.1–9.2 ? ?
α1A 6.6 ? ?
α1B 8.3 ? ?
α1D ? ? ?
α2A 1.9 ? ?
α2B 3.3 ? ?
α2C 1.4 ? ?
β1 3,100 ? ?
β2 2,700 ? ?
β3 271 ? ?
D1 2,779 ? ?
D2 1.2–5.0 ? Agonist
D3 6.4–16 ? ?
D4 8.7 ? ?
D5 ? ? ?
H1 ? ? ?
mACh ? ? ?
Notes: All receptors are human except 5-HT3 (rat/mouse), 5-HT4 (guinea pig), 5-HT5B (rat—no human counterpart), α1A-adrenergic (rat/human), and α2A-adrenergic (rat/human).[13]


Oral bioavailability is poor and it is not available in oral form in the US. DHE is available as a nasal spray and in ampules for subcutaneous, intramuscular and intravenous injection. Efficacy is variable in the nasal spray form with relative bioavailability of 32% compared to injection.


Dihydroergotamine (DHE) is a semi-synthetic form of ergotamine approved in the US in 1946.

Society and culture

Brand names

Brand names of DHE include Diergo, Dihydergot, D.H.E. 45, Ergont, Ikaran, Migranal, Orstanorm, and Seglor, among others.[15]

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).[16]


  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 "Dihydroergotamine Monograph for Professionals". Drugs.com. Archived from the original on 6 March 2021. Retrieved 23 July 2021.
  2. 2.0 2.1 2.2 Shafqat, R; Flores-Montanez, Y; Delbono, V; Nahas, SJ (2020). "Updated Evaluation of IV Dihydroergotamine (DHE) for Refractory Migraine: Patient Selection and Special Considerations". Journal of pain research. 13: 859–864. doi:10.2147/JPR.S203650. PMID 32431533.
  3. 3.0 3.1 3.2 3.3 Levin, Morris (8 May 2008). Comprehensive Review of Headache Medicine. Oxford University Press, USA. p. 217. ISBN 978-0-19-536673-0. Archived from the original on 28 August 2021. Retrieved 23 July 2021.
  4. 4.0 4.1 4.2 4.3 Silberstein, SD; Shrewsbury, SB; Hoekman, J (January 2020). "Dihydroergotamine (DHE) - Then and Now: A Narrative Review". Headache. 60 (1): 40–57. doi:10.1111/head.13700. PMID 31737909.
  5. 5.0 5.1 "Dihydroergotamine Mesylate Prices and Dihydroergotamine Mesylate Coupons - GoodRx". GoodRx. Retrieved 23 July 2021.
  6. "Dihydroergotamine Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 7 August 2019. Retrieved 23 July 2021.
  7. Singh, Mamta; Bhatia, Rohit (April 2011). Emergencies in Neurology. Byword Books Private Limited. p. 155. ISBN 978-81-8193-067-5. Archived from the original on 2021-08-29. Retrieved 2021-07-23.
  8. Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH (April 2005). "Parenteral dihydroergotamine for acute migraine headache: a systematic review of the literature". Annals of Emergency Medicine. 45 (4): 393–401. doi:10.1016/j.annemergmed.2004.07.430. PMID 15795718.
  9. Saper JR, Silberstein S, Dodick D, Rapoport A (November 2006). "DHE in the pharmacotherapy of migraine: potential for a larger role". Headache. 46 Suppl 4 (Suppl 4): S212-20. doi:10.1111/j.1526-4610.2006.00605.x. PMID 17078853. S2CID 34332034.
  10. 10.0 10.1 Schaerlinger B, Hickel P, Etienne N, Guesnier L, Maroteaux L (September 2003). "Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy". Br J Pharmacol. 140 (2): 277–84. doi:10.1038/sj.bjp.0705437. PMC 1574033. PMID 12970106.
  11. Silberstein SD, McCrory DC (February 2003). "Ergotamine and dihydroergotamine: history, pharmacology, and efficacy". Headache. 43 (2): 144–66. doi:10.1046/j.1526-4610.2003.03034.x. PMID 12558771. S2CID 21356727.
  12. Cavero I, Guillon JM (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". J Pharmacol Toxicol Methods. 69 (2): 150–61. doi:10.1016/j.vascn.2013.12.004. PMID 24361689.
  13. 13.0 13.1 https://web.archive.org/web/20210413101932/https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Ergotamine&doQuery=Submit+Query
  14. Silberstein SD, McCrory DC (February 2003). "Ergotamine and dihydroergotamine: history, pharmacology, and efficacy". Headache. 43 (2): 144–66. doi:10.1046/j.1526-4610.2003.03034.x. PMID 12558771.
  15. Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 340–. ISBN 978-3-88763-075-1. Archived from the original on 2021-04-13. Retrieved 2021-04-13.
  16. Restrictions on use of medicines containing ergot derivatives (EMA 2013) Archived 2018-06-20 at the Wayback Machine, Retrieved 3 August 2014

External links