Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an

ergot Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''. The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...

alkaloid used to treat

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

s. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of

sumatriptan Sumatriptan, sold commonly under brand names Imitrex and Treximet among others, is a medication used to treat migraine headaches and cluster headaches. It is taken orally, intranasally, or by subcutaneous injection. Therapeutic effects gen ...

. Nausea is a common side effect. It has similar actions to the triptans, acting as an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

to the serotonin receptors and causing vasoconstriction of the intracranial blood vessels, but also interacts centrally with

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

and adrenergic receptors. It can be used to treat acute

intractable Intractable may refer to: * Intractable conflict, a form of complex, severe, and enduring conflict * Intractable pain, pain which cannot be controlled/cured by any known treatment * Intractable problem In theoretical computer science and mathema ...

headache or

withdrawal Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * ''Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from a ban ...

from analgesics.

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 Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

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

Side effects

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.

Contraindications

DHE is contraindicated with potent

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

inhibitors, like macrolide antibiotics.

Pharmacology

Mechanism of action

DHE's antimigraine activity is due to its action as an agonist at the

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

5-HT_1B, 5-HT_1D, and 5-HT_1F receptors. It also interacts with other serotonin, adrenergic, and dopamine receptors. DHE is an agonist of the serotonin 5-HT_2B receptor and has been associated with cardiac valvulopathy.

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 Subcutaneous may refer to: * Subcutaneous injection * Subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The ...

, intramuscular and

intravenous injection Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...

. Efficacy is variable in the nasal spray form with relative bioavailability of 32% compared to injection.

Contraindications

Contraindications for DHE include: pregnancy, renal or hepatic failure, coronary, cerebral, and peripheral vascular disease, hypersensitivity reactions, sepsis, and uncontrolled

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

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 The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

’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 Ergotism (pron. ) is the effect of long-term ergot poisoning, traditionally due to the ingestion of the alkaloids produced by the ''Claviceps purpurea'' fungus—from the Latin "club" or clavus "nail" and for "head", i.e. the purple club-head ...

) 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