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Dihydroergotamine (/daɪˌhaɪdroʊ.ɜːrˈɡɒtəmiːn/ dy-HY-droh-ur-GOT-ə-meen; 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.

Description

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 the product, now known as Semprana, for nearly $1 billion but the FDA has rejected it 3 times due to quality control issues and it has yet to gain approval.

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]

References

^ ^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.
^ 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.
^ 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 1574033. PMID 12970106.
^ Restrictions on use of medicines containing ergot derivatives (EMA 2013), Retrieved 3 August 2014

External links

DHE prescribing information
Migranal prescribing information

UpToDate Contents

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1. 成人における片頭痛の急性期治療 acute treatment of migraine in adults
2. 薬物乱用頭痛：治療および予後 medication overuse headache treatment and prognosis
3. 小児における片頭痛の急性期治療 acute treatment of migraine in children
4. 慢性片頭痛 chronic migraine
5. 群発頭痛：治療および予後 cluster headache treatment and prognosis

English Journal

Pediatric inpatient headache therapy: What is available.

Kabbouche M1.
Headache.Headache.2015 Oct 31. doi: 10.1111/head.12701. [Epub ahead of print]
Status migrainosus is defined by the international classification of headache disorders (ICHD) criteria as a debilitating migraine lasting more then 72 hours. The epidemiology of status migrainosus is still unknown in adult and children, and frequently underdiagnosed. Children and adolescents often
PMID 26517974

Exacerbation of SUNCT and SUNA syndromes during intravenous dihydroergotamine treatment: A case series.

Lambru G1, Shanahan P2, Matharu M3.
Cephalalgia : an international journal of headache.Cephalalgia.2015 Oct;35(12):1115-24. doi: 10.1177/0333102415570495. Epub 2015 Feb 9.
BACKGROUND: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and with short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) remains challenging in view of the limited understanding of their pathop
PMID 25667300

Japanese Journal

amezinium metilsulfate と dihydroergotamine mesylate の併用が有効であった食後性低血圧の1例

安達典子,近藤昭,林恭一
日本老年医学会雑誌 36(7), 499-502, 1999-07-25
NAID 10008485159

片頭痛に起因する難治性小児めまい例

金谷浩一郎,福井加寿子,沖中芳彦,今手祐二,山下裕司
耳鼻咽喉科臨床 92(7), 707-712, 1999-07-01
… In contrast, Adenosine Triphosphate Disodium was somewhat effective, and Dihydroergotamine Mesylate was remarkably effective. …
NAID 10005265835

★リンクテーブル★

リンク元	「D.H.E」「DHE」「MIGRANAL」
関連記事	「mesylate」「dihydroergotamine」

「D.H.E」

Dihydroergotamine
Systematic (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
Clinical data
Trade names	D.H.E. 45, Migranal
AHFS/Drugs.com	monograph
MedlinePlus	a603022
License data	US FDA: Dihydroergotamine;
Pregnancy; category	US: X (Contraindicated); ;
Routes of; administration	nasal spray, SC, IM, IV
Legal status
Legal status	US: ℞-only;
Pharmacokinetic data
Bioavailability	32% Nasal Spary
Biological half-life	9 hours
Excretion	Bile
Identifiers
CAS Number	511-12-6
ATC code	N02CA01 (WHO)
PubChem	CID 10531
IUPHAR/BPS	121
DrugBank	DB00320
ChemSpider	10091
UNII	436O5HM03C
KEGG	D07837
ChEBI	CHEBI:4562
ChEMBL	CHEMBL1732
Synonyms	(5'α)-9,10-dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trione
Chemical data
Formula	C33H37N5O5
Molar mass	583.678 g/mol
	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 ; Key:LUZRJRNZXALNLM-JGRZULCMSA-N ;
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