Dihydroergotamine

Clinical data
Pronunciation	/daɪˌhaɪdroʊ.ɜːrˈɡɒtəmiːn/dy-HY-droh-ur-GOT-ə-meen
Trade names	D.H.E. 45, others
Other names	DHE; (5'α)-9,10-Dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trione
AHFS/Drugs.com	Monograph
MedlinePlus	a603022
License data	US DailyMed: Dihydroergotamine
Routes of administration	Nasal,subcutaneous,intramuscular,intravenous
ATC code	N02CA01 (WHO)
Legal status
Legal status	BR: Class D1 (Drug precursors)[1] US: ℞-only[2][3][4][5][6][7]
Pharmacokinetic data
Bioavailability	32% (nasal spray)
Eliminationhalf-life	9 hours
Excretion	Bile duct
Identifiers
IUPAC name (2R,4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),9,12,14-tetraene-4-carboxamide
CAS Number	511-12-6 mesylate: 6190-39-2
PubChemCID	10531
IUPHAR/BPS	121
DrugBank	DB00320 mesylate: DBSALT000997
ChemSpider	10091 mesylate: 64311
UNII	436O5HM03C mesylate: 81AXN7R2QT
KEGG	D07837 mesylate: D02211
ChEBI	CHEBI:4562 mesylate: CHEBI:59756
ChEMBL	ChEMBL1732 mesylate: ChEMBL1200517
CompTox Dashboard(EPA)	DTXSID6045614
ECHA InfoCard	100.007.386
Chemical and physical data
Formula	C33H37N5O5
Molar mass	583.689 g·mol−1
3D model (JSmol)	Interactive image
SMILES [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 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 Key:LUZRJRNZXALNLM-JGRZULCMSA-N

Dihydroergotamine (DHE), sold under the brand namesD.H.E. 45 andMigranal among others, is anergot alkaloid used to treatmigraines.^[8] It is a derivative ofergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that ofsumatriptan. Nausea is a common side effect.^[9]

It has similar actions to thetriptans, acting as anagonist to theserotonin receptors and causingvasoconstriction of theintracranial blood vessels, but also interacts centrally withdopamine andadrenergic receptors. It can be used to treat acuteintractable headache orwithdrawal fromanalgesics.

Subcutaneous and intramuscular injections are generally more effective than the nasal spray and can be self-administered by patients.^[9] Intravenous injection is considered very effective for severe migraine orstatus migrainosus. Dihydroergotamine is also used in the treatment ofmedication overuse headache.^[10]

Dihydroergotamine isindicated for the acute treatment of migraine.^[6][7]

Nausea is a common side effect of intravenous administration and less common in other modes.^[11]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.^[12] DHE produces no dependence.^[13]

Dihydroergotamine is contraindicated with potentCYP3A4 inhibitors, likemacrolide antibiotics.^[14]

Contraindications for dihydroergotamine include:pregnancy, kidney failure orliver failure, coronary, cerebral, andperipheral vascular disease, hypersensitivity reactions,sepsis, and uncontrolledhypertension.^[14]

Dihydroergotamine's antimigraine activity is due to its action as an agonist at theserotonin5-HT_1B,5-HT_1D, and5-HT_1F receptors. It also interacts with other serotonin,adrenergic, anddopamine receptors.^[15]

Dihydroergotamine is an agonist of the serotonin5-HT_2B receptor and has been associated withcardiac valvulopathy.^[16]

In spite of acting as an agonist of the serotonin5-HT_2A receptor, dihydroergotamine has been described as non-hallucinogenic.^[17] This is also the case with certain otherergolinederivatives, such asbromocriptine andpergolide.^[18]

Efficacy is variable in thenasal spray form with relative bioavailability of 32% compared to injection.^[21]

Dihydroergotamine is a semi-synthetic form of ergotamine approved in the US in 1946.^[21] Dihydroergotamine is derived from ergot, a fungus that grows on rye and other grains.^[22][23]

In 2013, theCommittee for Medicinal Products for Human Use of theEuropean 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 offibrosis andergotism) were said to be greater than the benefits in these indications.^[24][25][26]

Brand names of dihydroergotamine include Diergo, Dihydergot, D.H.E. 45, Ergont, Ikaran, Migranal, Orstanorm, and Seglor, among others.^[8]

• 5-HT1A agonists
• 5-HT2B agonists
• Alpha-1 blockers
• Alpha2-adrenergic agonists
• Antimigraine drugs
• Cardiotoxins
• Ergopeptines
• GABAA receptor positive allosteric modulators
• Lactams
• Non-hallucinogenic 5-HT2A receptor agonists
• Oxazolopyrrolopyrazines
• Serotonin receptor agonists

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