Dihydroergotamine

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Dihydroergotamine
Dihydroergotamine.svg
Clinical data
Pronunciation /dˌhdr.ɜːrˈɡɒtəmn/ dy-HY-droh-ur-GOT-ə-meen
Trade names D.H.E. 45, Migranal, others
Synonyms (5'α)-9,10-dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trione
AHFS/Drugs.com Monograph
MedlinePlus a603022
License data
Pregnancy
category
  • US: X (Contraindicated)
Routes of
administration
nasal spray, SC, IM, IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 32% Nasal Spary
Elimination half-life 9 hours
Excretion Bile
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.007.386 Edit this at Wikidata
Chemical and physical data
Formula C33H37N5O5
Molar mass 583.678 g/mol
3D model (JSmol)
  (verify)

Dihydroergotamine (DHE) 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 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.

Medical uses[edit]

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]

Side effects[edit]

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.[3]

Mechanism of action[edit]

DHE's antimigraine activity is due to its action as an agonist to the serotonin (5-HT) -1B, -1D and -1F receptors. It also interacts with other serotonin, adrenergic and dopamine receptors.[4]

History[edit]

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

Society and culture[edit]

Availability[edit]

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 bioavailability 32% of injectable administration.

European Union[edit]

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.[5]

References[edit]

  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. doi:10.1016/j.annemergmed.2004.07.430. PMID 15795718. 
  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. doi:10.1111/j.1526-4610.2006.00605.x. PMID 17078853. 
  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. doi:10.1038/sj.bjp.0705437. PMC 1574033Freely accessible. PMID 12970106. 
  4. ^ Silberstein, Stephen D.; McCrory, Douglas C. (2003-02-01). "Ergotamine and dihydroergotamine: history, pharmacology, and efficacy". Headache. 43 (2): 144–166. doi:10.1046/j.1526-4610.2003.03034.x. ISSN 0017-8748. PMID 12558771. 
  5. ^ Restrictions on use of medicines containing ergot derivatives (EMA 2013), Retrieved 3 August 2014

External links[edit]