dihydroergotamine   Click here for help

GtoPdb Ligand ID: 121

Synonyms: D.H.E. 45® | Migranal®
Approved drug PDB Ligand
dihydroergotamine is an approved drug (FDA (1997))
Compound class: Synthetic organic
Comment: Dihydroergotamine is an ergot alkaloid. It is used as a vasoconstrictor. The drug is administered as dihydroergotamine mesylate (PubChem CID 71171). The use of ergot alkaloids in the clinic has been discontinued or restricted due to their propensity to cause fibrosis.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 118.21
Molecular weight 583.28
XLogP 2.29
No. Lipinski's rules broken 0
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Canonical SMILES CN1CC(CC2C1Cc1c[nH]c3c1c2ccc3)C(=O)NC1(C)OC2(N(C1=O)C(Cc1ccccc1)C(=O)N1C2CCC1)O
Isomeric SMILES CN1C[C@@H](C[C@H]2[C@H]1Cc1c[nH]c3c1c2ccc3)C(=O)N[C@]1(C)O[C@@]2(N(C1=O)[C@@H](Cc1ccccc1)C(=O)N1[C@H]2CCC1)O
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
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Summary of Clinical Use Click here for help
Dihydroergotamine is used to treat migraine and cluster headaches. In 2020, a nasally administered dry-powder formulation of dihydroergotamine (STS101; Satsuma Pharmaceuticals) failed to show efficacy above placebo in phase 3 trial, as a treatment for acute migraine. STS101 was intended to improve upon the bioavailability and pharmacokinetics of the nasally administered formulation of dihydroergotamine in Migranal®.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The anti-migraine activity of dihydroergotamine is believed to be due to its high affinity binding to serotonin 5-HT1D receptors on intracranial blood vessels (causes vasoconstriction and headache relief) and on sensory nerve endings of the trigeminal system (inhibits release of pro-inflammatory neuropeptides)
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04406649 A Study to Evaluate the Safety of STS101 in the Acute Treatment of Migraine Phase 3 Interventional Satsuma Pharmaceuticals, Inc.
NCT03901482 A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate STS101 in the Acute Treatment of Migraine Phase 3 Interventional Satsuma Pharmaceuticals, Inc.
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