Record Information |
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Version | 2.0 |
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Creation Date | 2009-07-21 20:26:35 UTC |
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Update Date | 2014-12-24 20:25:51 UTC |
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Accession Number | T3D2750 |
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Identification |
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Common Name | Dihydroergotamine |
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Class | Small Molecule |
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Description | Dihydroergotamine is only found in individuals that have used or taken this drug. It is a 9,10alpha-dihydro derivative of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine disorders. Two theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine: 1) 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 and 2) activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release. |
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Compound Type | - Amide
- Amine
- Analgesic
- Analgesic, Non-Narcotic
- Anti-Migraine Agent
- Dopamine Agonist
- Drug
- Ether
- Metabolite
- Organic Compound
- Sympatholytic
- Synthetic Compound
- Vasoconstrictor Agent
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Chemical Structure | |
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Synonyms | Synonym | (2R,4R,7R)-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]-6-methyl-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),9,12,14-tetraene-4-carboxamide | 5'-Benzyl-12'-hydroxy-2'-methyl-3',6',18-trioxo-9,10-dihydroergotaman | 9,10-dihydro-12'-Hydroxy-2'-methyl-5'-(phenylmethyl)ergotoman-3',6',18-trione | 9,10-Dihydro-ergotamine | 9,10-dihydroergotamine | D.H.E. 45 | Dihidroergotamina | Dihydergot | Dihydroergotamin | Dihydroergotamine mesylate | Dihydroergotamine methanesulfonate | Dihydroergotamine monomethanesulfonate | Dihydroergotaminum | Diidroergotamina | Ergont | Ergotonin | Ikaran | Migranal | Orstanorm | Verladyn |
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Chemical Formula | C33H37N5O5 |
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Average Molecular Mass | 583.677 g/mol |
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Monoisotopic Mass | 583.279 g/mol |
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CAS Registry Number | 6190-39-2 |
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IUPAC Name | (2R,4R,7R)-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]-6-methyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),9,12,14-tetraene-4-carboxamide |
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Traditional Name | dihydroergotamine |
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SMILES | [H][C@@]12CCCN1C(=O)[C@]([H])(CC1=CC=CC=C1)N1C(=O)[C@@](C)(O[C@@]21O)N=C(O)[C@@]1([H])CN(C)[C@]2([H])CC3=CNC4=CC=CC(=C34)[C@@]2([H])C1 |
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InChI Identifier | 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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InChI Key | InChIKey=LUZRJRNZXALNLM-JGRZULCMSA-N |
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Chemical Taxonomy |
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Description | belongs to the class of organic compounds known as ergotamines, dihydroergotamines, and derivatives. These are organic compounds containing an ergotamine moiety, which is structurally characterized by a benzyl substituent attached to the piperazine ring of the ergopeptine backbone. |
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Kingdom | Organic compounds |
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Super Class | Alkaloids and derivatives |
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Class | Ergoline and derivatives |
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Sub Class | Lysergic acids and derivatives |
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Direct Parent | Ergotamines, dihydroergotamines, and derivatives |
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Alternative Parents | |
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Substituents | - Dihydroergotamine
- Ergotamine
- Hybrid peptide
- Alpha-dipeptide
- Lysergic acid amide
- Indoloquinoline
- Benzoquinoline
- Quinoline-3-carboxamide
- N-acyl-alpha amino acid or derivatives
- Pyrroloquinoline
- Alpha-amino acid or derivatives
- Quinoline
- 3-alkylindole
- Indole
- Indole or derivatives
- Isoindole or derivatives
- Piperidinecarboxamide
- 3-piperidinecarboxamide
- Aralkylamine
- N-alkylpiperazine
- Benzenoid
- Monocyclic benzene moiety
- 1,4-diazinane
- Oxazolidinone
- Piperazine
- Piperidine
- Tertiary carboxylic acid amide
- Heteroaromatic compound
- Oxazolidine
- Pyrrolidine
- Pyrrole
- Amino acid or derivatives
- Lactam
- Tertiary aliphatic amine
- Secondary carboxylic acid amide
- Orthocarboxylic acid derivative
- Carboxamide group
- Tertiary amine
- Oxacycle
- Organoheterocyclic compound
- Azacycle
- Alkanolamine
- Carboxylic acid derivative
- Organonitrogen compound
- Organic oxygen compound
- Organopnictogen compound
- Carbonyl group
- Organic nitrogen compound
- Amine
- Organooxygen compound
- Organic oxide
- Hydrocarbon derivative
- Aromatic heteropolycyclic compound
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Molecular Framework | Aromatic heteropolycyclic compounds |
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External Descriptors | |
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Biological Properties |
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Status | Detected and Not Quantified |
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Origin | Exogenous |
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Cellular Locations | - Cytoplasm
- Extracellular
- Membrane
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Biofluid Locations | Not Available |
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Tissue Locations | Not Available |
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Pathways | Not Available |
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Applications | |
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Biological Roles | |
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Chemical Roles | Not Available |
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Physical Properties |
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State | Solid |
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Appearance | White powder. |
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Experimental Properties | Property | Value |
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Melting Point | Not Available | Boiling Point | Not Available | Solubility | 2.29e-01 g/L | LogP | 2 |
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Predicted Properties | |
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Spectra |
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Spectra | Spectrum Type | Description | Splash Key | Deposition Date | View |
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Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0fr5-5891210000-f53c38352e2598f9007e | 2017-09-01 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive | splash10-0fdn-7491022000-6c73d0337e04ab2f6918 | 2017-10-06 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS ("Dihydroergotamine,1TMS,#1" TMS) - 70eV, Positive | Not Available | 2021-10-14 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive | Not Available | 2021-10-15 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive | Not Available | 2021-10-15 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive | Not Available | 2021-10-15 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive | Not Available | 2021-10-15 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive | Not Available | 2021-10-15 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-001i-0022090000-bfd200952b03e8b137ff | 2016-08-01 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0un9-0091010000-c5661ba02ab58100d046 | 2016-08-01 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-004i-4590000000-dc4a0cca36e4ae6c18c5 | 2016-08-01 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0019-0049160000-4fdc70b6d84db2eb175e | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-03xr-2196220000-3c3fcf127102792f663c | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0g4j-9810000000-88f13186254d2bf07e89 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-001i-0000090000-3abf973bfa14967f7f1d | 2021-09-22 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-001i-0010290000-1037c6e147fa5f93e653 | 2021-09-22 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-004i-0090010000-f5347f35594f87c4297f | 2021-09-22 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-001i-0000090000-10b01aae8e192c05edc6 | 2021-09-22 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-001i-2100390000-475a2b73d09ae5f9c174 | 2021-09-22 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0v03-9351430000-9c41d997e0687489c4ee | 2021-09-22 | View Spectrum |
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Toxicity Profile |
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Route of Exposure | Intravenous (7); Nasal (7).
Interpatient variable and may be dependent on the administration technique |
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Mechanism of Toxicity | Two theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine: 1) 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 and 2) activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release. |
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Metabolism | Dihydroergotamine is metabolized in the liver, with metabolites predominantly excreted in the feces. (5)
Route of Elimination: The major excretory route of dihydroergotamine is via the bile in the feces.
Only 6%-7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection.
Half Life: 9 hours |
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Toxicity Values | Not Available |
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Lethal Dose | Not Available |
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Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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Uses/Sources | Dihydroergotamine is a 9,10alpha-dihydro derivative of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine disorders. Ergoline alkaloids occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. (8, 11) For the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. |
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Minimum Risk Level | Not Available |
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Health Effects | Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (1, 12) |
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Symptoms | Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (9, 12) |
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Treatment | Treatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (10, 12) |
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Normal Concentrations |
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| Not Available |
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Abnormal Concentrations |
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| Not Available |
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External Links |
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DrugBank ID | DB00320 |
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HMDB ID | HMDB14465 |
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PubChem Compound ID | 10531 |
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ChEMBL ID | CHEMBL1732 |
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ChemSpider ID | 10091 |
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KEGG ID | C07798 |
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UniProt ID | Not Available |
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OMIM ID | |
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ChEBI ID | 4562 |
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BioCyc ID | Not Available |
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CTD ID | Not Available |
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Stitch ID | Dihydroergotamine |
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PDB ID | Not Available |
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ACToR ID | Not Available |
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Wikipedia Link | Dihydroergotamine |
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References |
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Synthesis Reference | Not Available |
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MSDS | Link |
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General References | - Richard JL: Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. Epub 2007 Jul 31. [17719115 ]
- Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. [10418123 ]
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- Kvernmo T, Hartter S, Burger E: A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. [16982285 ]
- Saper JR, Silberstein S: Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine. Headache. 2006 Nov;46 Suppl 4:S171-81. [17078849 ]
- Silberstein SD: The pharmacology of ergotamine and dihydroergotamine. Headache. 1997;37 Suppl 1:S15-25. [9009470 ]
- Drugs.com [Link]
- Wikipedia. Ergoline. Last Updated 2 April 2010. [Link]
- Wikipedia. Ergotism. Last Updated 6 April 2010. [Link]
- Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. [Link]
- Wikipedia. Dihydroergotamine. Last Updated 3 April 2010. [Link]
- RxList: The Internet Drug Index (2010). D.H.E. 45 (Dihydroergotamine). [Link]
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Gene Regulation |
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Up-Regulated Genes | Not Available |
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Down-Regulated Genes | Not Available |
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