Dihydroergotamine

Các tên gọi khác (9 ) :

(2R,4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),9,12,14-tetraene-4-carboxamide
5'-Benzyl-12'-hydroxy-2'-methyl-3',6',18-trioxo-9,10-dihydroergotaman
9,10-dihydro-12'-Hydroxy-2'-methyl-5'-(phenylmethyl)ergotoman-3',6',18-trione
9,10-dihydroergotamine
Dihidroergotamina
Dihydroergotamin
Dihydroergotamine
Dihydroergotaminum
Diidroergotamina

Thuốc điều trị đau nửa đầu

Thuốc Gốc

Small Molecule

CAS: 6190-39-2

ATC: N02CA01

ĐG : Bedford Labs , http://www.bedfordlabs.com

CTHH: C₃₃H₃₇N₅O₅

PTK: 583.6774

A 9,10alpha-dihydro derivative of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine disorders. [PubChem]

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₃₃H₃₇N₅O₅

Phân tử khối

583.6774

Monoisotopic mass

583.279469319

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

InChI Key

InChIKey=LUZRJRNZXALNLM-JGRZULCMSA-N

IUPAC Name

(2R,4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraene-4-carboxamide

Traditional IUPAC Name

dihydroergotamine

SMILES

[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O

Độ hòa tan

2.29e-01 g/l

logP

logS

-3.4

pKa (strongest acidic)

9.71

pKa (Strongest Basic)

8.39

PSA

118.21 Å²

Refractivity

159.39 m³·mol^-1

Polarizability

63.3 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Dược Lực Học : Dihydroergotamine is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Dihydroergotamine binds with high affinity to 5-HT_1Da and 5-HT_1Db receptors. It also binds with high affinity to serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors, noradrenaline a2A, a2B and a receptors, and dopamine D2L and D3 receptors. The therapeutic activity of Dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT_1D receptors.

Cơ Chế Tác Dụng : A 9,10alpha-dihydro derivative of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine disorders. [PubChem] Two theories have been proposed to explain the efficacy of 5-HT_1D receptor agonists in migraine: 1) activation of 5-HT_1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache and 2) activation of 5-HT_1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

Dược Động Học :

▧ Absorption :
Interpatient variable and may be dependent on the administration technique
▧ Volume of Distribution :
* 800 L
▧ Protein binding :
93% (to plasma proteins)
▧ Metabolism :
Hepatic
▧ Route of Elimination :
The major excretory route of dihydroergotamine is via the bile in the feces. Only 6%-7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection.
▧ Half Life :
9 hours
▧ Clearance :
* 1.5 L/min

Độc Tính : Side effects include abdominal pain, abnormal speech, coma, confusion, convulsions, hallucinations, increase and/or decrease in blood pressure, nausea, numbness, tingling, pain, and a bluish color of your fingersand toes, slowed breathing, vomiting

Chỉ Định : For the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

Tương Tác Thuốc :

Acebutolol Ischemia with risk of gangrene
Almotriptan Possible severe and prolonged vasoconstriction
Amprenavir Amprenavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated.
Amyl Nitrite Possible antagonism of action
Atazanavir Atazanavir may increase the therapeutic and adverse effects of dihydroergotamine.
Atenolol Ischemia with risk of gangrene
Betaxolol Ischemia with risk of gangrene
Bevantolol Ischemia with risk of gangrene
Bisoprolol Ischemia with risk of gangrene
Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Carteolol Ischemia with risk of gangrene
Carvedilol Ischemia with risk of gangrene
Clarithromycin Risk of ergotism and severe ischemia with this association
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of dihydroergotamine by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dihydroergotamine if delavirdine is initiated, discontinued or dose changed.
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Efavirenz Efavirenze may increase the adverse/toxic effects of dihydroergotamine. Concomitant therapy is contraindicated.
Eletriptan Possible severe and prolonged vasoconstriction
Erythrityl Tetranitrate Possible antagonism of action
Erythromycin Possible ergotism and severe ischemia with this combination
Esmolol Ischemia with risk of gangrene
Fluconazole Possible ergotism and severe ischemia with this combination
Fluoxetine Possible ergotism and severe ischemia with this combination
Fluvoxamine Possible ergotism and severe ischemia with this combination
Fosamprenavir Amprenavir increases the effect and toxicity of ergot derivative
Frovatriptan Possible severe and prolonged vasoconstriction
Indinavir Indinavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated.
Isosorbide Dinitrate Possible antagonism of action
Isosorbide Mononitrate Possible antagonism of action
Itraconazole Possible ergotism and severe ischemia with this combination
Josamycin Possible ergotism and severe ischemia with this combination
Ketoconazole Possible ergotism and severe ischemia with this combination
Labetalol Ischemia with risk of gangrene
Metoprolol Ischemia with risk of gangrene
Nadolol Ischemia with risk of gangrene.
Naratriptan Naratriptan, a serotonin 5-HT1D receptor agonists, may increase the vasoconstricting effect of dihydroergotamine. Concomitant use of these two agents within 24 hours is contraindicated.
Nefazodone Possible ergotism and severe ischemia with this combination
Nelfinavir Nelfinavir increases the effect and toxicity of ergot derivative
Nitroglycerin Possible antagonism of action
Oxprenolol Ischemia with risk of gangrene
Penbutolol Ischemia with risk of gangrene
Pentaerythritol Tetranitrate Possible antagonism of action
Pindolol Ischemia with risk of gangrene
Posaconazole Contraindicated co-administration
Practolol Ischemia with risk of gangrene
Propranolol Ischemia with risk of gangrene
Ritonavir The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.
Rizatriptan Possible severe and prolonged vasoconstriction
Saquinavir The protease inhibitor, saquinavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.
Sibutramine Possible serotoninergic syndrome with this combination
Sotalol Ischemia with risk of gangrene
Sumatriptan Possible severe and prolonged vasoconstriction
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telithromycin Telithromycin may reduce clearance of Dihydroergotamine. Concomitant therapy is contraindicated.
Timolol Ischemia with risk of gangrene
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Dihydroergotamine. Concomitant therapy is contraindicated.
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Troleandomycin Possible ergotism and severe ischemia with this combination
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of dihydroergotamine by decreasing its metabolism. Concomitant therapy is contraindicated.
Zileuton Possible ergotism and severe ischemia with this combination
Zolmitriptan Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, dihydroergotamine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.

Liều Lượng & Cách Dùng : Liquid - Intravenous
Liquid - Nasal

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Dihydroergotamine Mesylate 1 mg/ml

Giá bán buôn : USD >3.9

Đơn vị tính : ml
Biệt dược thương mại : Dihydroergotamine (Dhe) 1 mg/ml

Giá bán buôn : USD >4.18

Đơn vị tính : ml
Biệt dược thương mại : Migranal 4 mg/ml Spray

Giá bán buôn : USD >11.17

Đơn vị tính : spray
Biệt dược thương mại : Dihydroergotamine Mesylate 1 mg/ml Solution 1ml Ampule

Giá bán buôn : USD >36.4

Đơn vị tính : ampule
Biệt dược thương mại : Dihydroergotamine 1 mg/ml am

Giá bán buôn : USD >38.0

Đơn vị tính : ml
Biệt dược thương mại : D.h.e.45 1 mg/ml ampul

Giá bán buôn : USD >54.46

Đơn vị tính : ml
Biệt dược thương mại : Migranal nasal spray

Giá bán buôn : USD >90.83

Đơn vị tính : ml
Biệt dược thương mại : Migranal 4 mg/ml Solution 1ml Glass Container

Giá bán buôn : USD >94.46

Đơn vị tính : container
Biệt dược thương mại : D.H.E. 45 1 mg/ml ampul

Giá bán buôn : USD >120.88

Đơn vị tính : ml
Biệt dược thương mại : D.H.E. 45 1 mg/ml Solution 1ml Ampule

Giá bán buôn : USD >124.61

Đơn vị tính : ampule

Nhà Sản Xuất

Công ty : Valeant

Sản phẩm biệt dược : D.H.E. 45
Công ty : Sandoz

Sản phẩm biệt dược : Dihydergot
Công ty : Sigmapharm

Sản phẩm biệt dược : Ergont
Công ty :

Sản phẩm biệt dược : Ergotonin
Công ty : Pierre Fabre

Sản phẩm biệt dược : Ikaran
Công ty : Valeant

Sản phẩm biệt dược : Migranal
Công ty : Amdipharm

Sản phẩm biệt dược : Orstanorm
Công ty : Verla

Sản phẩm biệt dược : Verladyn

Đóng gói

Công ty : Bedford Labs

Website : http://www.bedfordlabs.com
Công ty : Draxis Specialty Pharmaceuticals Inc.

Website : http://www.draxispharma.com
Công ty : Mipharm S.P.A.

Website : http://www.mipharm.it
Công ty : Novartis AG

Website : http://www.novartis.com
Công ty : Paddock Labs

Website : http://www.paddocklabs.com
Công ty : Prescript Pharmaceuticals

Website : http://www.prescript.net
Công ty : Valeant Ltd.

Website : http://www.valeant.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00320

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=10531

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507711

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07798

ChemSpider

http://www.chemspider.com/Chemical-Structure.10091.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0574-0850-05

PharmGKB

http://www.pharmgkb.org/drug/PA164743028

Wikipedia

http://en.wikipedia.org/wiki/Dihydroergotamine

RxList

http://www.rxlist.com/cgi/generic2/dihyergmes.htm

PDRhealth

http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mig1267.shtml

Drugs.com

http://www.drugs.com/cdi/dihydroergotamine.html

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