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Dihydroergotamine Mesylate (DHE; Migranal) is a naturally occuring ergot alkaloid widely used to treat migraines. It functions similarly to triptans, agonistically binding to serotonin receptors and causing intracranial blood vessel vasoconstriction. However, it also interacts centrally with dopamine and adrenergic receptors.
Physicochemical Properties
| Molecular Formula | C34H41N5O8S |
| Molecular Weight | 679.7830 |
| Exact Mass | 679.267 |
| Elemental Analysis | C, 60.07; H, 6.08; N, 10.30; O, 18.83; S, 4.72 |
| CAS # | 6190-39-2 |
| Related CAS # | 511-12-6; 6190-39-2 (mesylate); |
| PubChem CID | 71171 |
| Appearance | White to off-white solid powder |
| Boiling Point | 1001.8ºC at 760 mmHg |
| Melting Point | 232°C |
| Flash Point | 559.7ºC |
| Index of Refraction | -20 ° (C=0.25, JP Method) |
| LogP | 2.87 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 48 |
| Complexity | 1260 |
| Defined Atom Stereocenter Count | 7 |
| SMILES | C[C@@]1(C(=O)N2[C@H](C(=O)N3CCC[C@H]3[C@@]2(O1)O)CC4=CC=CC=C4)NC(=O)[C@@H]5C[C@H]6[C@@H](CC7=CNC8=CC=CC6=C78)N(C5)C.CS(=O)(=O)O |
| InChi Key | ADYPXRFPBQGGAH-UMYZUSPBSA-N |
| InChi Code | InChI=1S/C33H37N5O5.CH4O3S/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;1-5(2,3)4/h3-6,8-11,17,21,23,25-27,34,42H,7,12-16,18H2,1-2H3,(H,35,39);1H3,(H,2,3,4)/t21-,23-,25-,26+,27+,32-,33+;/m1./s1 |
| Chemical Name | (6aR,9R,10aR)-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]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide;methanesulfonic acid |
| Synonyms | Dihydroergotamine Mesylate; DHE Migranal |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of dihydroergotamine during breastfeeding. Because it might cause adverse effects in the infant and decrease the milk supply, most authorities consider ergotamine to be contraindicated during nursing. The manufacturer of the dihydroergotamine nasal spray recommends that nursing mother should not breastfeed during treatment and for 3 days after the last dose. Any milk that is pumped during this time should be discarded. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
[1]. Parenteral dihydroergotamine for acute migraine headache: a systematic review of the literature. Ann Emerg Med, 2005. 45(4): p. 393-401. [2]. DHE in the pharmacotherapy of migraine: potential for a larger role. Headache, 2006. 46 Suppl 4: p. S212-20. [3]. Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy. Br J Pharmacol, 2003. 140(2): p. 277-84. [4]. Dihydroergotamine Tartrate Induces Lung Cancer Cell Death through Apoptosis and Mitophagy. Chemotherapy. 2016;61(6):304-12. [5]. Dihydroergotamine mesylate enhances the anti-tumor effect of sorafenib in liver cancer cells. Biochem Pharmacol. 2023 May;211:115538. |
| Additional Infomation |
Dihydroergotamine Mesylate can cause developmental toxicity according to state or federal government labeling requirements. Dihydroergotamine mesylate is the methanesulfonic acid salt of dihydroergotamine, a semisynthetic ergot alkaloid with weaker oxytocic and vasoconstrictor properties than ergotamine. Both the mesylate and the tartrate salts are used for the treatment of migraine and orthostatic hypotension. It has a role as a serotonergic agonist, a non-narcotic analgesic and a vasoconstrictor agent. It contains a dihydroergotamine. Dihydroergotamine Mesylate is an ergot derivative with agonistic activity for alpha-adrenergic, serotonergic, and dopaminergic receptors. Dihydroergotamine mesylate most likely relieves migraine headaches by binding to and stimulating the 5-HT1D receptor subtype, thereby causing constriction of cerebral blood vessels. However, it has also been proposed that dihydroergotamine mesylate acts upon 5-HT1D receptors on sensory nerve endings of the trigeminal system, thereby decreasing the release of pro-inflammatory neuropeptide release. A 9,10alpha-dihydro derivative of ERGOTAMINE. It is used as a vasoconstrictor, specifically for the therapy of MIGRAINE DISORDERS. See also: Dihydroergotamine (has active moiety) ... View More ... |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~73.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (3.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4711 mL | 7.3553 mL | 14.7106 mL | |
| 5 mM | 0.2942 mL | 1.4711 mL | 2.9421 mL | |
| 10 mM | 0.1471 mL | 0.7355 mL | 1.4711 mL |