Peringatan Keamanan

Symptoms of overdose include numbness, tingling, pain, and cyanosis of the extremities associated with diminished or absent peripheral pulses; respiratory depression; an increase and/or decrease in blood pressure, usually in that order; confusion, delirium, convulsions, and coma; and/or some degree of nausea, vomiting, and abdominal pain.L38469 In case of overdose, warmth should be applied to affected areas and vasodilators administered. Local poison control centres should be contacted for detailed information on care in cases of ergot overdose.

Dihydroergotamine

DB00320

small molecule approved investigational

Deskripsi

A 9,10alpha-dihydro derivative of ergotamine. Dihydroergotamine is used as an abortive therapy for migraines.L38469 Its use has largely been supplanted by triptans in current therapy due to the class's greater selectivity and more favourable side effect profile.

Recent improvements have been made in the design of intranasal delivery devices allowing for greater delivery of dihydroergotamine solution to the vasculature-rich upper nasal cavity.A239569 The recently approved Precision Olfactory Delivery technology developed by Impel Neuropharma technology has correlated with an increase of 3-fold in Cmax and 4-fold in AUC despite the solution formulated at 75% of the strength of the existing intranasal product.

Struktur Molekul 2D

Berat 583.6774
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) DHE exhibits a biphasic elimination with half lives of 0.7-1 h and 10-13 h. [A239234]
Volume Distribusi DHE has a steady-state volume of distribution of 800 L.[L38469, L38459]
Klirens (Clearance) The total clearance of DHE is 1.5 L/h with renal clearance contributing 0.1 L/h.[L38469]

Absorpsi

When delivered intranasally, DHE has a bioavailability of approximately 40% with a tmax of 30-60 min.L38469, A239234. Oral formulations have largely been unsuccessful due to a 1% bioavailability owing to a high degree of first-pass metabolism. A239234 Both intramuscular and intravenous administration produces 100% bioavailability with a tmax of 1-2 min and 24-34 min respectively.A239234, A239424

Metabolisme

DHE is metabolized in the liver to four identified metabolites. 8'-?-hydroxy dihydroergotamine is the primary metabolite and an active one with equipotency for adrenergic and 5-HT receptors.L38469 8'-?-hydroxy dihydroergotamine is present at plasma concentrations 5-7 times that of DHE. A239234 The remaining metabolites are Dihydrolysergic acid, dihydrolysergic amide, and a fourth metabolite formed through oxidative opening of the proline ring are considered minor metabolites. After intranasal administration, it has been found that metabolites represent 20-30% of plasma AUC.L38469, A239234

Rute Eliminasi

DHE is primarily eliminated through hepatic metabolism followed by biliary excretion. L38469, A239234 6-7% of a single intramuscular dose is excreted in the urine.A239234

Interaksi Makanan

1 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits the metabolism of dihydroergotamine through the CYP3A4 pathway and, therefore, may increase serum levels of dihydroergotamine. Use caution if co-administering.

Interaksi Obat

1550 Data
Modafinil The metabolism of Dihydroergotamine can be increased when combined with Modafinil.
Armodafinil The metabolism of Dihydroergotamine can be increased when combined with Armodafinil.
Valsartan Dihydroergotamine may decrease the antihypertensive activities of Valsartan.
Ramipril Dihydroergotamine may decrease the antihypertensive activities of Ramipril.
Remikiren Dihydroergotamine may decrease the antihypertensive activities of Remikiren.
Torasemide Dihydroergotamine may decrease the antihypertensive activities of Torasemide.
Guanadrel Dihydroergotamine may decrease the antihypertensive activities of Guanadrel.
Olmesartan Dihydroergotamine may decrease the antihypertensive activities of Olmesartan.
Chlorthalidone Dihydroergotamine may decrease the antihypertensive activities of Chlorthalidone.
Nitroprusside Dihydroergotamine may decrease the antihypertensive activities of Nitroprusside.
Minoxidil Dihydroergotamine may decrease the antihypertensive activities of Minoxidil.
Treprostinil Dihydroergotamine may decrease the antihypertensive activities of Treprostinil.
Bendroflumethiazide Dihydroergotamine may decrease the antihypertensive activities of Bendroflumethiazide.
Fosinopril Dihydroergotamine may decrease the antihypertensive activities of Fosinopril.
Trandolapril Dihydroergotamine may decrease the antihypertensive activities of Trandolapril.
Metolazone Dihydroergotamine may decrease the antihypertensive activities of Metolazone.
Benazepril Dihydroergotamine may decrease the antihypertensive activities of Benazepril.
Cyclothiazide Dihydroergotamine may decrease the antihypertensive activities of Cyclothiazide.
Candoxatril Dihydroergotamine may decrease the antihypertensive activities of Candoxatril.
Mecamylamine Dihydroergotamine may decrease the antihypertensive activities of Mecamylamine.
Moexipril Dihydroergotamine may decrease the antihypertensive activities of Moexipril.
Lisinopril Dihydroergotamine may decrease the antihypertensive activities of Lisinopril.
Hydroflumethiazide Dihydroergotamine may decrease the antihypertensive activities of Hydroflumethiazide.
Cryptenamine Dihydroergotamine may decrease the antihypertensive activities of Cryptenamine.
Perindopril Dihydroergotamine may decrease the antihypertensive activities of Perindopril.
Candesartan cilexetil Dihydroergotamine may decrease the antihypertensive activities of Candesartan cilexetil.
Eprosartan Dihydroergotamine may decrease the antihypertensive activities of Eprosartan.
Chlorothiazide Dihydroergotamine may decrease the antihypertensive activities of Chlorothiazide.
Quinapril Dihydroergotamine may decrease the antihypertensive activities of Quinapril.
Telmisartan Dihydroergotamine may decrease the antihypertensive activities of Telmisartan.
Hydrochlorothiazide Dihydroergotamine may decrease the antihypertensive activities of Hydrochlorothiazide.
Trichlormethiazide Dihydroergotamine may decrease the antihypertensive activities of Trichlormethiazide.
Deserpidine Dihydroergotamine may decrease the antihypertensive activities of Deserpidine.
Pentolinium Dihydroergotamine may decrease the antihypertensive activities of Pentolinium.
Trimethaphan Dihydroergotamine may decrease the antihypertensive activities of Trimethaphan.
Diazoxide Dihydroergotamine may decrease the antihypertensive activities of Diazoxide.
Bretylium Dihydroergotamine may decrease the antihypertensive activities of Bretylium.
Captopril Dihydroergotamine may decrease the antihypertensive activities of Captopril.
Epoprostenol Dihydroergotamine may decrease the antihypertensive activities of Epoprostenol.
Polythiazide Dihydroergotamine may decrease the antihypertensive activities of Polythiazide.
Cilazapril Dihydroergotamine may decrease the antihypertensive activities of Cilazapril.
Saprisartan Dihydroergotamine may decrease the antihypertensive activities of Saprisartan.
Spirapril Dihydroergotamine may decrease the antihypertensive activities of Spirapril.
Tienilic acid Dihydroergotamine may decrease the antihypertensive activities of Tienilic acid.
Diethylnorspermine Dihydroergotamine may decrease the antihypertensive activities of Diethylnorspermine.
Temocapril Dihydroergotamine may decrease the antihypertensive activities of Temocapril.
Nicorandil Dihydroergotamine may decrease the antihypertensive activities of Nicorandil.
Rauwolfia serpentina root Dihydroergotamine may decrease the antihypertensive activities of Rauwolfia serpentina root.
Enalaprilat Dihydroergotamine may decrease the antihypertensive activities of Enalaprilat.
Angiotensin 1-7 Dihydroergotamine may decrease the antihypertensive activities of Angiotensin 1-7.
Imidapril Dihydroergotamine may decrease the antihypertensive activities of Imidapril.
BQ-123 Dihydroergotamine may decrease the antihypertensive activities of BQ-123.
Cicletanine Dihydroergotamine may decrease the antihypertensive activities of Cicletanine.
Dihydralazine Dihydroergotamine may decrease the antihypertensive activities of Dihydralazine.
Zofenopril Dihydroergotamine may decrease the antihypertensive activities of Zofenopril.
Guanoxan Dihydroergotamine may decrease the antihypertensive activities of Guanoxan.
Delapril Dihydroergotamine may decrease the antihypertensive activities of Delapril.
Vincamine Dihydroergotamine may decrease the antihypertensive activities of Vincamine.
Linsidomine Dihydroergotamine may decrease the antihypertensive activities of Linsidomine.
Guanoxabenz Dihydroergotamine may decrease the antihypertensive activities of Guanoxabenz.
Tolonidine Dihydroergotamine may decrease the antihypertensive activities of Tolonidine.
Endralazine Dihydroergotamine may decrease the antihypertensive activities of Endralazine.
Cadralazine Dihydroergotamine may decrease the antihypertensive activities of Cadralazine.
Cyclopenthiazide Dihydroergotamine may decrease the antihypertensive activities of Cyclopenthiazide.
Bietaserpine Dihydroergotamine may decrease the antihypertensive activities of Bietaserpine.
Guanazodine Dihydroergotamine may decrease the antihypertensive activities of Guanazodine.
Methoserpidine Dihydroergotamine may decrease the antihypertensive activities of Methoserpidine.
Guanoclor Dihydroergotamine may decrease the antihypertensive activities of Guanoclor.
Muzolimine Dihydroergotamine may decrease the antihypertensive activities of Muzolimine.
Xipamide Dihydroergotamine may decrease the antihypertensive activities of Xipamide.
Candesartan Dihydroergotamine may decrease the antihypertensive activities of Candesartan.
Tocopherylquinone Dihydroergotamine may decrease the antihypertensive activities of Tocopherylquinone.
Benazeprilat Dihydroergotamine may decrease the antihypertensive activities of Benazeprilat.
Fosinoprilat Dihydroergotamine may decrease the antihypertensive activities of Fosinoprilat.
Ramiprilat Dihydroergotamine may decrease the antihypertensive activities of Ramiprilat.
Perindoprilat Dihydroergotamine may decrease the antihypertensive activities of Perindoprilat.
Quinaprilat Dihydroergotamine may decrease the antihypertensive activities of Quinaprilat.
Furosemide Dihydroergotamine may decrease the antihypertensive activities of Furosemide.
Enalapril Dihydroergotamine may decrease the antihypertensive activities of Enalapril.
Indapamide Dihydroergotamine may decrease the antihypertensive activities of Indapamide.
Guanethidine Dihydroergotamine may decrease the antihypertensive activities of Guanethidine.
Pinacidil Dihydroergotamine may decrease the antihypertensive activities of Pinacidil.
Riociguat Dihydroergotamine may decrease the antihypertensive activities of Riociguat.
Macitentan Dihydroergotamine may decrease the antihypertensive activities of Macitentan.
Aliskiren Dihydroergotamine may decrease the antihypertensive activities of Aliskiren.
Debrisoquine Dihydroergotamine may decrease the antihypertensive activities of Debrisoquine.
Ambrisentan Dihydroergotamine may decrease the antihypertensive activities of Ambrisentan.
Selexipag Dihydroergotamine may decrease the antihypertensive activities of Selexipag.
Eplerenone Dihydroergotamine may decrease the antihypertensive activities of Eplerenone.
Buthiazide Dihydroergotamine may decrease the antihypertensive activities of Buthiazide.
Azilsartan medoxomil Dihydroergotamine may decrease the antihypertensive activities of Azilsartan medoxomil.
Buprenorphine Dihydroergotamine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Dihydroergotamine.
Dronabinol The serum concentration of Dronabinol can be increased when it is combined with Dihydroergotamine.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Dihydroergotamine.
Hydrocodone Dihydroergotamine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Hydroxyzine Hydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Dihydroergotamine.
Magnesium sulfate The therapeutic efficacy of Dihydroergotamine can be increased when used in combination with Magnesium sulfate.
Methotrimeprazine Dihydroergotamine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Metyrosine Dihydroergotamine may increase the sedative activities of Metyrosine.

Target Protein

5-hydroxytryptamine receptor 1B HTR1B
5-hydroxytryptamine receptor 1D HTR1D
5-hydroxytryptamine receptor 1F HTR1F
D(2) dopamine receptor DRD2
Alpha-2A adrenergic receptor ADRA2A
5-hydroxytryptamine receptor 1A HTR1A
5-hydroxytryptamine receptor 1E HTR1E
5-hydroxytryptamine receptor 2A HTR2A
5-hydroxytryptamine receptor 2B HTR2B
5-hydroxytryptamine receptor 2C HTR2C
Alpha-1 adrenergic receptors ADRA1A
Alpha-2 adrenergic receptors ADRA2A
D(3) dopamine receptor DRD3
D(4) dopamine receptor DRD4
5-hydroxytryptamine receptor 4 HTR4
Beta-3 adrenergic receptor ADRB3

Referensi & Sumber

Artikel (PubMed)
  • PMID: 18179563
    Shrewsbury SB, Cook RO, Taylor G, Edwards C, Ramadan NM: Safety and pharmacokinetics of dihydroergotamine mesylate administered via a Novel (Tempo) inhaler. Headache. 2008 Mar;48(3):355-67. doi: 10.1111/j.1526-4610.2007.01006.x. Epub 2007 Dec 28.
  • PMID: 29229375
    Charles A: The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018 Feb;17(2):174-182. doi: 10.1016/S1474-4422(17)30435-0. Epub 2017 Dec 8.
  • PMID: 23815106
    Ramirez Rosas MB, Labruijere S, Villalon CM, Maassen Vandenbrink A: Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs. Expert Opin Pharmacother. 2013 Aug;14(12):1599-610. doi: 10.1517/14656566.2013.806487. Epub 2013 Jul 2.
  • PMID: 22444161
    Dahlof C, Maassen Van Den Brink A: Dihydroergotamine, ergotamine, methysergide and sumatriptan - basic science in relation to migraine treatment. Headache. 2012 Apr;52(4):707-14. doi: 10.1111/j.1526-4610.2012.02124.x. Epub 2012 Mar 22.
  • PMID: 32078320
    Sullivan HJ, Tursi A, Moore K, Campbell A, Floyd C, Wu C: Binding Interactions of Ergotamine and Dihydroergotamine to 5-Hydroxytryptamine Receptor 1B (5-HT1b) Using Molecular Dynamics Simulations and Dynamic Network Analysis. J Chem Inf Model. 2020 Mar 23;60(3):1749-1765. doi: 10.1021/acs.jcim.9b01082. Epub 2020 Mar 2.
  • PMID: 23620146
    Silberstein SD, Kori SH: Dihydroergotamine: a review of formulation approaches for the acute treatment of migraine. CNS Drugs. 2013 May;27(5):385-94. doi: 10.1007/s40263-013-0061-2.
  • PMID: 31737909
    Silberstein SD, Shrewsbury SB, Hoekman J: Dihydroergotamine (DHE) - Then and Now: A Narrative Review. Headache. 2020 Jan;60(1):40-57. doi: 10.1111/head.13700. Epub 2019 Nov 17.

Contoh Produk & Brand

Produk: 28 • International brands: 7
Produk
  • D.H.E. 45
    Injection, solution • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Approved
  • D.H.E. 45
    Injection, solution • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Approved
  • Dihydroergotamine (dhe), 1mg/ml
    Liquid • 1 mg / mL • Intramuscular; Intravenous; Subcutaneous • Canada • Approved
  • Dihydroergotamine Mesylate
    Injection • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
  • Dihydroergotamine Mesylate
    Injection, solution • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
  • Dihydroergotamine Mesylate
    Injection, solution • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
  • Dihydroergotamine Mesylate
    Injection • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
  • Dihydroergotamine Mesylate
    Spray • 4 mg/1mL • Nasal • US • Generic • Approved
Menampilkan 8 dari 28 produk.
International Brands
  • Dihydergot — Sandoz
  • Ergont — Sigmapharm
  • Ergotonin
  • Ikaran — Pierre Fabre
  • Orstanorm — Amdipharm
  • Trudhesa — Impel NeuroPharma, Inc.
  • Verladyn — Verla

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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