Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of

ergotamine Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural sim ...

. 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 Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, ...

, acting as an agonist to the

serotonin receptors 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

and causing

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...

of the

intracranial The cranial cavity, also known as intracranial space, is the space within the skull that accommodates the brain. The skull minus the mandible is called the ''cranium''. The cavity is formed by eight cranial bones known as the neurocranium that in ...

blood vessels, but also interacts centrally with dopamine and

adrenergic receptors The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

. It can be used to treat acute intractable headache or withdrawal from

analgesics An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

Medical uses

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 A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, c ...

Side effects

Nausea is a common side effect of IV administration and less common in other modes.

Antiemetics An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be ...

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.

Contraindications

DHE is contraindicated with potent CYP3A4 inhibitors, like

macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Ma ...

antibiotics.

Pharmacology

Mechanism of action

DHE's antimigraine activity is due to its action as an agonist at the serotonin 5-HT_1B, 5-HT_1D, and 5-HT_1F receptors. It also interacts with other serotonin,

adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

, and

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

s. DHE is an agonist of the serotonin 5-HT_2B receptor and has been associated with

cardiac valvulopathy Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic ...

Pharmacodynamic

Pharmacokinetics

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 Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

and intravenous injection. Efficacy is variable in the

nasal spray Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for syst ...

form with relative bioavailability of 32% compared to injection.

Contraindications

Contraindications for DHE include:

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

, renal or hepatic failure, coronary, cerebral, and

peripheral vascular disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular dise ...

, hypersensitivity reactions,

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

, and uncontrolled hypertension.

History

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.

European Union

In 2013 the European Medicines Agency’s

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...

(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 Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

and ergotism) were said to be greater than the benefits in these indications.Restrictions on use of medicines containing ergot derivatives (EMA 2013)
Retrieved 3 August 2014

References

External links

* * {{Portal bar , Medicine Alpha-1 blockers Alpha-2 adrenergic receptor agonists Antimigraine drugs GABAA receptor positive allosteric modulators Lactams Lysergamides Oxazolopyrrolopyrazines Serotonin receptor agonists