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Identification
Name Ergoloid mesylate
Accession Number DB01049 (APRD00711)
Type small molecule
Groups approved
Description

Ergoloid mesylate is a dihydrogenated ergot (Claviceps purpurea) derivative alkaloid used as a vasodilator agent. Ergoloid Mesylate is the only vasodilator that has shown mild benefits in the treatment of vascular dementia.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Alkergot
Circanol
Co-Dergocrine Mesylate
Deapril-ST
Dihydroergotoxin Mesilat
Dihydroergotoxin Mesylate
Dihydroergotoxin Methanesulfonate
Dihydroergotoxine Mesilate
Dihydroergotoxine Mesylate
Dihydroergotoxine Methanesulfonate
Dihydroergotoxine Methanesulphonate
Ergoloid Mesylates [Usan]
Gerimal
Hydergin
Hydergine
Hydergine LC
Hydrogenated Ergot Alkaloids
Ischelium
Redergin
Trigot
First Prev Next Last
Brand mixtures Not Available
Categories
  • Sympatholytics
  • Vasodilator Agents
  • Adrenergic alpha-Antagonists
  • Nootropic Agents
CAS number 8067-24-1
Weight Average: 631.74
Monoisotopic: 631.267584003
Chemical Formula C30H41N5O8S
InChI Key InChIKey=FQHMMOGHDWAXDI-WUQHHHCFSA-N
InChI
InChI=1S/C29H37N5O5.CH4O3S/c1-15(2)28(27(37)34-16(3)26(36)33-10-6-9-23(33)29(34,38)39-28)31-25(35)18-11-20-19-7-5-8-21-24(19)17(13-30-21)12-22(20)32(4)14-18;1-5(2,3)4/h5,7-8,13,15-16,18,20,22-23,30,38H,6,9-12,14H2,1-4H3,(H,31,35);1H3,(H,2,3,4)/t16-,18+,20+,22+,23-,28+,29-;/m0./s1
Plain Text
IUPAC Name
(2R,4R,7R)-N-[(1S,2S,4R,7S)-2-hydroxy-7-methyl-5,8-dioxo-4-(propan-2-yl)-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraene-4-carboxamide; methanesulfonic acid
SMILES
CS(O)(=O)=O.[H][C@@]12CCCN1C(=O)[C@H](C)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)(O[C@@]21O)C(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For use as an adjunct therapy for patients with dementia
Pharmacodynamics Ergoloid Mesylate may increase cerebral metabolism and blood flow. The role of this medication in the therapy of dementia is controversial. A recent controlled study in patients with Alzheimer's disease found that there was no advantage to the use of ergoloid mesylates compared to placebo, suggesting that ergoloid mesylates may lower scores on some cognitive and behavioral rating scales. Further study is needed to determine the risk-benefit profile of ergoloid mesylates in the treatment of dementia.
Mechanism of action Ergoloid mesylates act centrally, decreasing vascular tone and slowing the heart rate, and acts peripherally to block alpha-receptors. One other possible mechanism is the effect of ergoloid mesylates on neuronal cell metabolism, resulting in improved oxygen uptake and cerebral metabolism, thereby normalizing depressed neurotransmitter levels.
Absorption Rapidly but incompletely (approximately 25%) absorbed from the gastrointestinal tract. Approximately 50% of the absorbed dose is eliminated by first-pass metabolism.
Volume of distribution Not Available
Protein binding 98-99%
Metabolism Hepatic.
Route of elimination Not Available
Half life 3.5 hours
Clearance Not Available
Toxicity Symptoms of overdose include dyspnea, hypotension or hypertension, rapid weak pulse, delirium, nausea, vomiting, and bradycardia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Mutual pharmaceutical co inc
  • Watson laboratories inc
  • Sandoz inc
  • 3m pharmaceuticals inc
  • Bristol myers squibb co pharmaceutical research institute
  • Kv pharmaceutical co
  • Lederle laboratories div american cyanamid co
  • Superpharm corp
  • Vangard laboratories inc div midway medical co
  • Ivax pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Ergoloid mesylates powder 87.5 USD g
Ergoloid mesylates 1 mg tablet 1.3 USD tablet
Hydergine 1 mg Tablet 1.1 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP 2.8 Not Available
Predicted Properties
Property Value Source
logP 2.17 ChemAxon
pKa (strongest acidic) 9.71 ChemAxon
pKa (strongest basic) 8.39 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 118.21 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 143.66 ChemAxon
polarizability 57.99 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02268 Link_out
KEGG Compound C14055 Link_out
ChEBI 34706 Link_out
ChEMBL 34706 Link_out
Therapeutic Targets Database DAP000901 Link_out
PharmGKB PA164752439 Link_out
Drug Product Database 176176 Link_out
Wikipedia http://en.wikipedia.org/wiki/Ergoloid Link_out
ATC Codes
  • C04AE01
AHFS Codes
  • 12:16.00
PDB Entries Not Available
FDA label Not Available
MSDS show (72.9 KB)
Interactions
Drug Interactions
Drug Interaction
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Telithromycin Telithromycin may reduce clearance of Ergoloid mesylates. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Ergoloid mesylates if Telithromycin is initiated, discontinued or dose changed.
Tipranavir Tipranavir may increase the plasma concentration of Ergoloid mesylates. Concomitant therapy should be avoided.
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ergoloid mesylates by decreasing their metabolism. Concomitant therapy is contraindicated.
Zolmitriptan Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, ergoloid mesylate, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
Food Interactions Not Available
Targets

1. Alpha-2A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Markstein R: Hydergine: interaction with the neurotransmitter systems in the central nervous system. J Pharmacol. 1985;16 Suppl 3:1-17. Pubmed

2. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Markstein R: Hydergine: interaction with the neurotransmitter systems in the central nervous system. J Pharmacol. 1985;16 Suppl 3:1-17. Pubmed

3. Solute carrier organic anion transporter family member 2B1

Pharmacological action: yes
Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost

Organism class: human
UniProt ID: O94956 Link_out
Gene: SLCO2B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lu WJ, Huang JD, Lai ML: The effects of ergoloid mesylates and ginkgo biloba on the pharmacokinetics of ticlopidine. J Clin Pharmacol. 2006 Jun;46(6):628-34. Pubmed

4. 5-hydroxytryptamine 1A receptor

Pharmacological action: unknown
Actions: other

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Korneyev AY, Cincotta AH: Identification of hepatic, non-monoamine, dihydroergocryptine binding sites with significant gender differences. Life Sci. 1996;58(12):241-8. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Althaus M, Retzow A, Castell JV, Gomez-Lechon MJ, Amalou Z, Rose T, Appel K: In vitro identification of the cytochrome P450 isoform responsible for the metabolism of alpha-dihydroergocryptine. Xenobiotica. 2000 Nov;30(11):1033-45. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19