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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
Structure of DIHYDROERGOTAMINE TARTRATE

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

HIDE SMILES / InChI

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.

Originator

Curator's Comment: Dihydroergotamine was synthesized (using hydrogenation [reduction] of the double bond at the 9- 10 position of the ergoline ring of E) by Stoll and Hofmann in 1943.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
D.H.E. 45

Approved Use

Dihydroergotamine 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 Date

1946
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.02 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
5.05 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
7.952 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
7%
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

Doses

DosePopulationAdverse 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)
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)
Sources:
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)
Vomiting (3 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
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

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
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 Fri Dec 15 18:37:34 GMT 2023
Edited
by admin
on Fri Dec 15 18:37:34 GMT 2023
Record UNII
76F2R89O7X
Record Status Validated (UNII)
Record Version
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Name Type Language
DIHYDROERGOTAMINE TARTRATE
WHO-DD  
Common Name English
Dihydroergotamine tartrate [WHO-DD]
Common Name English
Code System Code Type Description
FDA UNII
76F2R89O7X
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
CAS
5989-77-5
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
RXCUI
236680
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY RxNorm
SMS_ID
100000087507
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
EVMPD
SUB01719MIG
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
EPA CompTox
DTXSID30859427
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
DRUG BANK
DBSALT001066
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
PUBCHEM
76963764
Created by admin on Fri Dec 15 18:37:34 GMT 2023 , Edited by admin on Fri Dec 15 18:37:34 GMT 2023
PRIMARY
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