Details
Stereochemistry | ABSOLUTE |
Molecular Formula | 4C33H37N5O5.C4H6O6 |
Molecular Weight | 2484.7964 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 30 / 30 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@H]([C@@H](O)C(O)=O)C(O)=O.[H][C@@]12CCCN1C(=O)[C@H](CC3=CC=CC=C3)N4C(=O)[C@](C)(NC(=O)[C@H]5CN(C)[C@]6([H])CC7=CNC8=CC=CC(=C78)[C@@]6([H])C5)O[C@@]24O.[H][C@@]9%10CCCN9C(=O)[C@H](CC%11=CC=CC=C%11)N%12C(=O)[C@](C)(NC(=O)[C@H]%13CN(C)[C@]%14([H])CC%15=CNC%16=CC=CC(=C%15%16)[C@@]%14([H])C%13)O[C@@]%10%12O.[H][C@@]%17%18CCCN%17C(=O)[C@H](CC%19=CC=CC=C%19)N%20C(=O)[C@](C)(NC(=O)[C@H]%21CN(C)[C@]%22([H])CC%23=CNC%24=CC=CC(=C%23%24)[C@@]%22([H])C%21)O[C@@]%18%20O.[H][C@@]%25%26CCCN%25C(=O)[C@H](CC%27=CC=CC=C%27)N%28C(=O)[C@](C)(NC(=O)[C@H]%29CN(C)[C@]%30([H])CC%31=CNC%32=CC=CC(=C%31%32)[C@@]%30([H])C%29)O[C@@]%26%28O
InChI
InChIKey=FXDJFTCVYTUARH-YZPGULDNSA-N
InChI=1S/4C33H37N5O5.C4H6O6/c4*1-32(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;5-1(3(7)8)2(6)4(9)10/h4*3-6,8-11,17,21,23,25-27,34,42H,7,12-16,18H2,1-2H3,(H,35,39);1-2,5-6H,(H,7,8)(H,9,10)/t4*21-,23-,25-,26+,27+,32-,33+;1-,2-/m11111/s1
Molecular Formula | C33H37N5O5 |
Molecular Weight | 583.6774 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 7 / 7 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | C4H6O6 |
Molecular Weight | 150.0868 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Dihydroergotamine (DHE) is a semisynthetic, hydrogenated ergot alkaloid,
synthesized by reducing an unsaturated bond in ergotamine. Dihydroergotamine was originally envisaged as an antihypertensive agent, but it was later shown to be highly effective in treating migraine.
Dihydroergotamine was first used to treat migraine in 1945 by Horton, Peters, and Blumenthal at the Mayo Clinic. In 1986, Raskin and Callaham reconfirmed
the effectiveness of DHE for both intermittent and intractable migraine. The use of DHE was reviewed by Scott in 1992. In 1997, a nasal spray
version was approved for use in migraine. 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-HT1Dα and 5-HT1Dβ receptors. It also binds with high
affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α, receptors, and dopamine D2L and D3 receptors.
The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine. One theory suggests that activation of 5-HT1D receptors located on
intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of
5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of proinflammatory neuropeptide release.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.5 nM [IC50] | |||
0.7 nM [IC50] | |||
0.4 nM [IC50] | |||
9.0 nM [IC50] | |||
1.3 nM [IC50] | |||
Target ID: CHEMBL1805 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12558771 |
180.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | D.H.E. 45 Approved UseDihydroergotamine Mesylate Injection, USP is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Launch Date1946 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.02 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8841149/ |
1 mg single, nasal dose: 1 mg route of administration: Nasal experiment type: SINGLE co-administered: |
DIHYDROERGOTAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.05 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8841149/ |
1 mg single, nasal dose: 1 mg route of administration: Nasal experiment type: SINGLE co-administered: |
DIHYDROERGOTAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.952 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8841149/ |
1 mg single, nasal dose: 1 mg route of administration: Nasal experiment type: SINGLE co-administered: |
DIHYDROERGOTAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8841149/ |
1 mg single, nasal dose: 1 mg route of administration: Nasal experiment type: SINGLE co-administered: |
DIHYDROERGOTAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Disc. AE: Rhinitis, Dizziness... AEs leading to discontinuation/dose reduction: Rhinitis (2 patients) Sources: Dizziness (2 patients) Edema face (1 patient) Cold sweat (1 patient) Trauma (1 patient) Depression (1 patient) Somnolence (1 patient) Allergy (1 patient) Vomiting (1 patient) Hypotension (1 patient) Paraesthesia (1 patient) |
4 mg 1 times / day steady, intranasal Highest studied dose Dose: 4 mg, 1 times / day Route: intranasal Route: steady Dose: 4 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: migraine Age Group: adult Sex: unknown Sources: |
|
1 mg single, subcutaneous Recommended Dose: 1 mg Route: subcutaneous Route: single Dose: 1 mg Sources: |
unhealthy, adult Health Status: unhealthy Condition: migraine Age Group: adult Sex: unknown Sources: |
Disc. AE: Cerebrovascular event... AEs leading to discontinuation/dose reduction: Cerebrovascular event (grade 5) Sources: |
1 mg 1 times / day steady, subcutaneous (max) Recommended Dose: 1 mg, 1 times / day Route: subcutaneous Route: steady Dose: 1 mg, 1 times / day Sources: |
unhealthy, adult n = 51 Health Status: unhealthy Condition: migraine Age Group: adult Sex: unknown Population Size: 51 Sources: |
Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (20 patients) Sources: Vomiting (3 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Allergy | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Cold sweat | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Depression | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Edema face | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Hypotension | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Paraesthesia | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Somnolence | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Trauma | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Vomiting | 1 patient Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Dizziness | 2 patients Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Rhinitis | 2 patients Disc. AE |
2 mg single, intranasal Studied dose Dose: 2 mg Route: intranasal Route: single Dose: 2 mg Sources: |
unhealthy, 18 - 65 years n = 1796 Health Status: unhealthy Condition: migraine Age Group: 18 - 65 years Sex: M+F Population Size: 1796 Sources: |
Cerebrovascular event | grade 5 Disc. AE |
1 mg single, subcutaneous Recommended Dose: 1 mg Route: subcutaneous Route: single Dose: 1 mg Sources: |
unhealthy, adult Health Status: unhealthy Condition: migraine Age Group: adult Sex: unknown Sources: |
Nausea | 20 patients Disc. AE |
1 mg 1 times / day steady, subcutaneous (max) Recommended Dose: 1 mg, 1 times / day Route: subcutaneous Route: steady Dose: 1 mg, 1 times / day Sources: |
unhealthy, adult n = 51 Health Status: unhealthy Condition: migraine Age Group: adult Sex: unknown Population Size: 51 Sources: |
Vomiting | 3 patients Disc. AE |
1 mg 1 times / day steady, subcutaneous (max) Recommended Dose: 1 mg, 1 times / day Route: subcutaneous Route: steady Dose: 1 mg, 1 times / day Sources: |
unhealthy, adult n = 51 Health Status: unhealthy Condition: migraine Age Group: adult Sex: unknown Population Size: 51 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 12.6 uM] | ||||
yes [IC50 2.8 uM] | ||||
yes [IC50 49.9 uM] | ||||
Page: 5.0 |
yes [Ki 120 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Transient global amnesia, migraine, thalamic infarct, dihydroergotamine, and sumatriptan. | 2000 Apr |
|
Hydergine for dementia. | 2001 |
|
Management of hot flashes in breast-cancer survivors. | 2001 Apr |
|
[Cluster headache: clinical treatment]. | 2001 Apr 10 |
|
Current concepts of pelvic congestion and chronic pelvic pain. | 2001 Apr-Jun |
|
Treatment and management of cluster headache. | 2001 Feb |
|
[Treatment of cluster headache]. | 2001 Feb |
|
Ergot alkaloid transport across ruminant gastric tissues. | 2001 Feb |
|
Pharmacological characterisation of the decrease in 5-HT synthesis in the mouse brain evoked by the selective serotonin re-uptake inhibitor citalopram. | 2001 Feb |
|
A fresh look at migraine therapy. New treatments promise improved management. | 2001 Jan |
|
[Ormond's fibrosis, bone osteolysis and stomach intramural metastases in the course f low-differentiated prostatic cancer]. | 2001 Jul |
|
Effects of dihydroergotamine on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients undergoing craniotomy for brain tumors. | 2001 Jul |
|
Successful withdrawal from analgesic abuse in a group of youngsters with chronic daily headache. | 2001 Jun |
|
Complicated migraine and migraine variants. | 2001 Mar |
|
Status migrainosus in children and adolescents. | 2001 Mar |
|
Application of oxygen vectors to Claviceps purpurea cultivation. | 2001 May |
|
Saint-Anthony's fire. | 2001 Nov 17 |
|
Comparison of intravenous valproate versus intramuscular dihydroergotamine and metoclopramide for acute treatment of migraine headache. | 2001 Nov-Dec |
|
In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense. | 2001 Oct |
|
A simple thin-layer chromatographic method for the detection of ergovaline in leaf sheaths of tall fescue (Festuca arundinacea) infected with Neotyphodium coenophialum. | 2001 Sep |
|
An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. | 2002 |
|
[Acute renal failure caused by dihydroergotamine]. | 2002 |
|
Practical approaches to migraine management. | 2002 |
|
Frovatriptan: a review of drug-drug interactions. | 2002 Apr |
|
Specific labelling of serotonin 5-HT(1B) receptors in rat frontal cortex with the novel, phenylpiperazine derivative, [3H]GR125,743. A pharmacological characterization. | 2002 Apr |
|
Therapeutic strategies for orthostatic intolerance: mechanisms, observations, and making patients feel better. | 2002 Apr 1 |
|
Comparative effects of clonidine and dihydroergotamine on venomotor tone and orthostatic tolerance in patients with severe hypoadrenergic orthostatic hypotension. | 2002 Apr 1 |
|
Valvular heart disease in patients taking pergolide. | 2002 Dec |
|
Management of the acute migraine headache. | 2002 Dec 1 |
|
Ergotamine-induced anorectal strictures: report of five cases. | 2002 Feb |
|
Naratriptan in the prophylaxis of cluster headache. | 2002 Jan |
|
Syndrome of cerebrospinal fluid hypovolemia following lumbar puncture cerebrospinal fluid leak in a patient with idiopathic intracranial hypertension. | 2002 Jan |
|
[Treatment of migraine in patients with hypertension and ischemic heart disease]. | 2002 Jan 20 |
|
The effect of rizatriptan, ergotamine, and their combination on human peripheral arteries: a double-blind, placebo-controlled, crossover study in normal subjects. | 2002 Jul |
|
Fatal ergotism induced by an HIV protease inhibitor. | 2002 Jul-Aug |
|
Intravenous valproate sodium in the treatment of daily headache. | 2002 Jun |
|
Endocrine and respiratory responses to ergotamine in Brahman and Hereford steers. | 2002 Jun |
|
Cardiovascular, respiratory, and body temperature responses of sheep to the ergopeptides ergotamine and ergovaline. | 2002 Mar |
|
Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for dihydroergotamine and its major metabolite in human plasma. | 2002 Mar 5 |
|
[Use and misuse of triptans: a case report]. | 2002 Mar-Apr |
|
Wilfred Harris' early description of cluster headache. | 2002 May |
|
Incidence and determinants of migraine prophylactic medication in the Netherlands. | 2002 May |
|
Buccal absorption of ergotamine tartrate using the bioadhesive tablet system in guinea-pigs. | 2002 May 15 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/dihydroergotamine.html
Usual Adult Dose for Migraine
IM or subcutaneous: Initial dose: 1 mg given as quickly as possible after the first symptom of headache. Additional 1 mg doses can be given hourly until the headache has stopped or a total dose of 3 mg has been reached. The total weekly dose should not exceed 6 mg.
IV: Initial dose: 1 mg given as quickly as possible after the first symptom of headache. Additional 1 mg doses can be given hourly until the headache has stopped or a total dose of 2 mg has been reached. The total weekly dose should not exceed 6 mg.
Intranasal: 1 spray (0.5 mg) into each nostril (total = 1 mg). Repeat if needed within 15 minutes to a maximum of 4 sprays (2 mg) per day. The total weekly dose should not exceed 8 sprays (4 mg).
Usual Adult Dose for Cluster Headache
IM or subcutaneous: Initial dose: 1 mg given as quickly as possible after the first symptom of headache. Additional 1 mg doses can be given hourly until the headache has stopped or a total dose of 3 mg has been reached. The total weekly dose should not exceed 6 mg.
IV: Initial dose: 1 mg given as quickly as possible after the first symptom of headache. Additional 1 mg doses can be given hourly until the headache has stopped or a total dose of 2 mg has been reached. The total weekly dose should not exceed 6 mg.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12770948
Dihydroergotamine (DHE) (EC(50)=10.9+/-0.3 nM) and 8'-OH-DHE (EC(50)=30.4+/-0.8 nM) inhibited the firing of serotoninergic neurons in the rat dorsal raphe nucleus within brain stem slices.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 18:37:34 GMT 2023
by
admin
on
Fri Dec 15 18:37:34 GMT 2023
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Record UNII |
76F2R89O7X
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Record Status |
Validated (UNII)
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Record Version |
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76F2R89O7X
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5989-77-5
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236680
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100000087507
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SUB01719MIG
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DTXSID30859427
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DBSALT001066
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76963764
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