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 |
|
Ergotamine, dihydroergotamine: current uses and problems. | 2001 |
|
Clinical ergotism induced by ritonavir. | 2001 |
|
Sumatriptan by injection. | 2001 |
|
How it started. | 2001 |
|
Clinically significant drug interactions with agents specific for migraine attacks. | 2001 |
|
Management of hot flashes in breast-cancer survivors. | 2001 Apr |
|
[Cluster headache: clinical treatment]. | 2001 Apr 10 |
|
[Migraine: use of preventive agents]. | 2001 Apr 10 |
|
Current concepts of pelvic congestion and chronic pelvic pain. | 2001 Apr-Jun |
|
The first world report of botulinum A toxin injection for status migrainosus. | 2001 Aug |
|
Treatment and management of cluster headache. | 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 |
|
Patterns of ergotamine and sumatriptan use in the Netherlands from 1991 to 1997. | 2001 Jun |
|
Complicated migraine and migraine variants. | 2001 Mar |
|
Application of oxygen vectors to Claviceps purpurea cultivation. | 2001 May |
|
Ergotism related to interaction between nelfinavir and ergotamine. | 2001 May |
|
An unusual case of clarithromycin associated ergotism. | 2001 Nov |
|
Clinical features of withdrawal headache following overuse of triptans and other headache drugs. | 2001 Nov 13 |
|
Saint-Anthony's fire. | 2001 Nov 17 |
|
Migraines. | 2001 Nov-Dec |
|
Advances in pharmacological treatment of migraine. | 2001 Oct |
|
[Hemorrhagic diarrhea with competing etiologies]. | 2001 Oct 1 |
|
[Migraine and facial pain]. | 2001 Oct 15 |
|
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 |
|
[The problems of migraine headache treatment]. | 2002 |
|
Postoperative ileus: progress towards effective management. | 2002 |
|
An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. | 2002 |
|
Frovatriptan: a review of drug-drug interactions. | 2002 Apr |
|
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 |
|
Fibrosis due to ergot derivatives: exposure to risk should be weighed up. | 2002 Dec |
|
The antimigraine 5-HT 1B/1D receptor agonists, sumatriptan, zolmitriptan and dihydroergotamine, attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. | 2002 Dec |
|
Management of the acute migraine headache. | 2002 Dec 1 |
|
Syndrome of cerebrospinal fluid hypovolemia following lumbar puncture cerebrospinal fluid leak in a patient with idiopathic intracranial hypertension. | 2002 Jan |
|
Possible ergotamine-caffeine-associated delirium. | 2002 Jan |
|
Intravenous valproate sodium in the treatment of daily headache. | 2002 Jun |
|
Cardiovascular, respiratory, and body temperature responses of sheep to the ergopeptides ergotamine and ergovaline. | 2002 Mar |
|
Treatment patterns of isolated benign headache in US emergency departments. | 2002 Mar |
|
Fibrotic valvular heart disease subsequent to bromocriptine treatment. | 2002 Nov-Dec |
|
Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine. | 2002 Oct |
|
[Ergotism in a patient treated with ritonavir and ergotamine]. | 2002 Oct 26 |
|
Simplified extraction of ergovaline and peramine for analysis of tissue distribution in endophyte-infected grass tillers. | 2002 Oct 9 |
|
Drug combinations in the therapy of low response to phosphodiesterase 5 inhibitors in patients with erectile dysfunction. | 2002 Sep-Oct |
|
Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine. | 2003 |
|
Pharmacological characterization of 5-HT(1B) receptor-mediated inhibition of local excitatory synaptic transmission in the CA1 region of rat hippocampus. | 2003 Jan |
|
Variations among emergency departments in the treatment of benign headache. | 2003 Jan |
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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