dihydroergotamine dihydroergotamine 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. it is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. nausea is a common side effect. dihydroergotamineclinical datapronunciation/daɪˌhaɪdroʊ.ɜːrˈɡɒtəmiːn/ dy-hy-droh-ur-got-ə-meen trade namesd.h.e. 45, migranal, trudhesa, othersother namesdhe; (5'α)-9,10-dihydro-12'-hydroxy-2'-methyl-5'-(phenylmethyl)-ergotaman-3',6',18-trioneahfs/drugs.commonographmedlineplusa603022license data us fda: dihydroergotamine routes ofadministrationnasal, subcutaneous, intramuscular, intravenousatc coden02ca01 (who) legal statuslegal status us: ℞-only pharmacokinetic databioavailability32% (nasal spray)elimination half-life9 hoursexcretionbileidentifiers iupac name (2r,4r,7r)-n-dodecan-4-yl]-6-methyl-6,11-diazatetracyclohexadeca-1(16),9,12,14-tetraene-4-carboxamide cas number511-12-6 ymesylate: 6190-39-2 ypubchem cid10531iuphar/bps121drugbankdb00320 ymesylate: dbsalt000997chemspider10091 ymesylate: 64311unii436o5hm03cmesylate: 81axn7r2qt ykeggd07837 ymesylate: d02211chebichebi:4562 ymesylate: chebi:59756chemblchembl1732 ymesylate: chembl1200517comptox dashboard (epa)dtxsid6045614 echa infocard100.007.386 chemical and physical dataformulac33h37n5o5molar mass583.689 g·mol−13d model (jsmol)interactive image smiles 56c(c(=o)n1(c)o4(o)n(c1=o)(cc2ccccc2)c(=o)n3ccc34)cn(c)5()cc7cc8cccc6c78 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 ykey:luzrjrnzxalnlm-jgrzulcmsa-n y (verify) 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. 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. 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 inhibitors, like macrolide antibiotics. pharmacology mechanism of action 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. dhe is an agonist of the serotonin 5-ht2b receptor and has been associated with cardiac valvulopathy. pharmacodynamic activities of dihydroergotamine at various sites site affinity (ki/ic50 ) efficacy (emax ) action 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). 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 and intravenous injection. 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. 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 (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.