Dihydroergotamine

Dihydroergotamine

Clinical data
Pronunciation	/daɪˌhaɪdroʊ.ɜːrˈɡɒtəmiːn/ dy-HY-droh-ur-GOT-ə-meen
Trade names	D.H.E. 45, Migranal, others
AHFS/Drugs.com	Monograph
MedlinePlus	a603022
License data	US FDA: Dihydroergotamine
Pregnancy category	US: X (Contraindicated)
Routes of administration	nasal spray, SC, IM, IV
ATC code	N02CA01 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	32% Nasal Spary
Biological half-life	9 hours
Excretion	Bile
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
Synonyms	(5'α)-9,10-dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trione
CAS Number	511-12-6 Y
PubChem (CID)	10531
IUPHAR/BPS	121
DrugBank	DB00320 Y
ChemSpider	10091 Y
UNII	436O5HM03C Y
KEGG	D07837 Y
ChEBI	CHEBI:4562 Y
ChEMBL	CHEMBL1732 Y
ECHA InfoCard	100.025.669
Chemical and physical data
Formula	C33H37N5O5
Molar mass	583.678 g/mol
3D model (Jmol)	Interactive image
SMILES O=C3N1CCC[C@H]1[C@]2(O)O[C@](C(=O)N2[C@H]3Cc4ccccc4)(NC(=O)[C@@H]7C[C@@H]8c5cccc6c5c(cn6)C[C@H]8N(C)C7)C
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 Y Key:LUZRJRNZXALNLM-JGRZULCMSA-N Y

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.

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.

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. DHE is also used in the treatment of medication overuse headache.

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.

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.

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 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.

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.