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Pronunciation | /daɪˌhaɪdroʊ.ɜːrˈɡɒtəmiːn/ dy-HY-droh-ur-GOT-ə-meen |
Trade names | D.H.E. 45, Migranal, Trudhesa, 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 |
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Routes of administration | Nasal, Subcutaneous, Intramuscular, Intravenous |
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Pharmacokinetic data | |
Bioavailability | 32% (nasal spray) |
Elimination half-life | 9 hours |
Excretion | Bile |
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ECHA InfoCard | 100.007.386 |
Chemical and physical data | |
Formula | C33H37N5O5 |
Molar mass | 583.689 g·mol−1 |
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Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. [7] 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. [8]
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. [8] Intravenous injection is considered very effective for severe migraine or status migrainosus. DHE is also used in the treatment of medication overuse headache. [9]
Nausea is a common side effect of IV administration and less common in other modes. [10] 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. [11] DHE produces no dependence. [12]
DHE is contraindicated with potent CYP3A4 inhibitors, like macrolide antibiotics. [13]
DHE's antimigraine activity is due to its action as an agonist at the serotonin 5-HT1B, 5-HT1D, and 5-HT1F receptors. It also interacts with other serotonin, adrenergic, and dopamine receptors. [14]
DHE is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy. [15]
Site | Affinity (Ki/IC50 [nM]) | Efficacy (Emax [%]) | Action |
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5-HT1A | 0.4–1.5 | ? | Agonist |
5-HT1B | 0.006–18 | ? | Agonist |
5-HT1D | 0.13–0.5 | ? | Agonist |
5-HT1E | 1,100 | ? | ? |
5-HT1F | 180 | ? | Agonist |
5-HT2A | 9.0 | ? | Agonist |
5-HT2B | 15–33 | ? | Agonist |
5-HT2C | 1.3 | ? | Agonist |
5-HT3 | >3,700–>10,000 | ? | ? |
5-HT4 | 60 | ? | ? |
5-HT5A | ? | ? | ? |
5-HT5B | ? | ? | |
5-HT6 | 5.4 | ? | ? |
5-HT7 | 9.1–9.2 | ? | ? |
α1A | 6.6 | ? | ? |
α1B | 8.3 | ? | ? |
α1D | ? | ? | ? |
α2A | 1.9 | ? | ? |
α2B | 3.3 | ? | ? |
α2C | 1.4 | ? | ? |
β1 | 3,100 | ? | ? |
β2 | 2,700 | ? | ? |
β3 | 271 | ? | ? |
D1 | 2,779 | ? | ? |
D2 | 1.2–5.0 | ? | Agonist |
D3 | 6.4–16 | ? | ? |
D4 | 8.7 | ? | ? |
D5 | ? | ? | ? |
H1 | ? | ? | ? |
mACh | ? | ? | ? |
Notes: All receptors are human except 5-HT3 (rat/mouse), 5-HT4 (guinea pig), 5-HT5B (rat—no human counterpart), α1A-adrenergic (rat/human), and α2A-adrenergic (rat/human). [16] |
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 relative bioavailability of 32% compared to injection. [18]
Contraindications for DHE include: pregnancy, renal or hepatic failure, coronary, cerebral, and peripheral vascular disease, hypersensitivity reactions, sepsis, and uncontrolled hypertension. [13]
Dihydroergotamine (DHE) is a semi-synthetic form of ergotamine approved in the US in 1946. [19] Dihydroergotamine is derived from ergot, a fungus that grows on rye and other grains. [20] [21]
Brand names of DHE include Diergo, Dihydergot, D.H.E. 45, Ergont, Ikaran, Migranal, Orstanorm, and Seglor, among others. [7]
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. [22]
Sumatriptan, sold under the brand name Imitrex among others, is a medication used to treat migraine headaches and cluster headaches. It is taken orally, intranasally, or by subcutaneous injection. Therapeutic effects generally occur within three hours.
Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.
Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor. It is used for acute migraines, sometimes with caffeine as the combination ergotamine/caffeine.
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced dopamine synthesis in the substantia nigra of the brain. Pergolide acts on many of the same receptors as dopamine to increase receptor activity.
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, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.
Rizatriptan, sold under the brand name Maxalt among others, is a medication used for the treatment of migraine headaches. It is taken by mouth. It can also be applied on the tongue. It is a serotonin (5-HT) 1B/1D receptor agonist (triptan).
Zolmitriptan, sold under the brand name Zomig among others, is a triptan used in the acute treatment of migraine attacks with or without aura and cluster headaches. It is a selective serotonin receptor agonist of the 1B and 1D subtypes.
Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used either by mouth, by injection into a muscle, or injection into a vein. It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection. Effects last between 45 and 180 minutes.
Ergotamine/caffeine, sold under the brand name Cafergot among others, is a fixed-dose combination medication used for the treatment of migraine. It contains ergotamine, as the tartrate, an alpha adrenergic blocking agent; and caffeine, a cranial vasoconstrictor.
Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.
Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the market in the United States and Canada due to adverse effects. It is taken by mouth.
Almotriptan is a triptan medication discovered and developed by Almirall for the treatment of heavy migraine headache.
Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second-generation triptan medication intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc.
Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks.
Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They are selective 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D) agonists. Migraine is a complex disease which affects about 15% of the population and can be highly disabling. Triptans have advantages over ergotamine and dihydroergotamine, such as selective pharmacology, well established safety record and evidence-based prescribing instructions. Triptans are therefore often preferred treatment in migraine.
Migraine may be treated either prophylactically (preventive) or abortively (rescue) for acute attacks. Migraine is an complex condition; there are various preventive treatments which disrupt different links in the chain of events that occur during a migraine attack. Rescue treatments also target and disrupt different processes occurring during migraine.
Donitriptan (INN) is a triptan drug which was investigated as an antimigraine agent but ultimately was never marketed. It acts as a high-affinity, high-efficacy/near-full agonist of the 5-HT1B and 5-HT1D receptors, and is among the most potent of the triptan series of drugs. Donitriptan was being developed in France by bioMérieux-Pierre Fabre and made it to phase II clinical trials in Europe before development was discontinued.