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Identification
NameErgoloid mesylate
Accession NumberDB01049  (APRD00711, DB01287)
TypeSmall Molecule
GroupsApproved
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. Ergoloid Mesylate is a mixture of three different ergotamantriones: dihydroergocornine, dihydroergocristine, and dihydroergocryptine. It has been proposed to be a neuroprotective agent. The mechanism of its therapeutic actions is not clear.

Structure
Thumb
Synonyms
SynonymLanguageCode
co-dergocrine mesilateNot AvailableNot Available
co-dergocrine mesylateNot AvailableNot Available
co-dergocrine methanesulfonateNot AvailableNot Available
codergocrine mesilateNot AvailableNot Available
codergocrine mesylateNot AvailableNot Available
codergocrine methanesulfonateNot AvailableNot Available
Dihydroergotoxine MesilateNot AvailableNot Available
Dihydroergotoxine MesylateNot AvailableNot Available
dihydroergotoxine methanesulfonateNot AvailableNot Available
Dihydroergotoxine MethanesulfonateNot AvailableNot Available
dihydroergotoxine methanesulfonatesNot AvailableNot Available
dihydroergotoxine monomethanesulfonateNot AvailableNot Available
dihydrogenated ergot alkaloidsNot AvailableNot Available
Ergoloid MesylatesNot AvailableUSAN
ergoloid methanesulfonateNot AvailableNot Available
ergoloid methanesulfonatesNot AvailableNot Available
hydrogenated ergot alkaloidsNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AlkergotNot Available
GerimalNot Available
HydergineNot Available
Hydergine LCNot Available
Brand mixturesNot Available
Categories
CAS number8067-24-1
WeightAverage: 631.74
Monoisotopic: 631.267584003
Chemical FormulaC30H41N5O8S
InChI KeyFQHMMOGHDWAXDI-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
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
Mass SpecNot Available
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor use as an adjunct therapy for patients with dementia.
PharmacodynamicsErgoloid 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 actionErgoloid 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.
AbsorptionRapidly but incompletely (approximately 25%) absorbed from the gastrointestinal tract. Approximately 50% of the absorbed dose is eliminated by first-pass metabolism.
Volume of distributionNot Available
Protein binding98-99%
Metabolism

Hepatic.

Route of eliminationNot Available
Half life3.5 hours
ClearanceNot Available
ToxicitySymptoms of overdose include dyspnea, hypotension or hypertension, rapid weak pulse, delirium, nausea, vomiting, and bradycardia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8284
Blood Brain Barrier - 0.9494
Caco-2 permeable - 0.6447
P-glycoprotein substrate Substrate 0.6838
P-glycoprotein inhibitor I Inhibitor 0.6581
P-glycoprotein inhibitor II Non-inhibitor 0.8001
Renal organic cation transporter Non-inhibitor 0.8838
CYP450 2C9 substrate Non-substrate 0.75
CYP450 2D6 substrate Non-substrate 0.7966
CYP450 3A4 substrate Substrate 0.6681
CYP450 1A2 substrate Non-inhibitor 0.7702
CYP450 2C9 substrate Non-inhibitor 0.7072
CYP450 2D6 substrate Non-inhibitor 0.9221
CYP450 2C19 substrate Non-inhibitor 0.6493
CYP450 3A4 substrate Non-inhibitor 0.7973
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8464
Ames test Non AMES toxic 0.6324
Carcinogenicity Non-carcinogens 0.6535
Biodegradation Not ready biodegradable 0.9321
Rat acute toxicity 2.5438 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8821
hERG inhibition (predictor II) Inhibitor 0.5783
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
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Ergoloid mesylates powder87.5USDg
Ergoloid mesylates 1 mg tablet1.3USDtablet
Hydergine 1 mg Tablet1.1USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP2.8Not Available
Predicted Properties
PropertyValueSource
logP2.17ChemAxon
pKa (Strongest Acidic)9.71ChemAxon
pKa (Strongest Basic)8.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.21 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity143.66 m3·mol-1ChemAxon
Polarizability57.99 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02268
KEGG CompoundC14055
ChEBI34706
ChEMBL
Therapeutic Targets DatabaseDAP000901
PharmGKBPA164752439
Drug Product Database176176
WikipediaErgoloid
ATC CodesC04AE01
AHFS Codes
  • 12:16.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.9 KB)
Interactions
Drug Interactions
Drug
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TelithromycinTelithromycin 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.
TipranavirTipranavir may increase the plasma concentration of Ergoloid mesylates. Concomitant therapy should be avoided.
TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TranylcypromineIncreased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ergoloid mesylates by decreasing their metabolism. Concomitant therapy is contraindicated.
ZolmitriptanConcomitant 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 InteractionsNot Available

Targets

1. Alpha-2 adrenergic receptor

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details
Alpha-2B adrenergic receptor P18089 Details
Alpha-2C adrenergic receptor P18825 Details

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-1 adrenergic receptor

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details
Alpha-1B adrenergic receptor P35368 Details
Alpha-1D adrenergic receptor P25100 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 2B1 O94956 Details

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. Serotonin Receptors

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details
5-hydroxytryptamine receptor 1B P28222 Details
5-hydroxytryptamine receptor 1D P28221 Details
5-hydroxytryptamine receptor 1E P28566 Details
5-hydroxytryptamine receptor 1F P30939 Details
5-hydroxytryptamine receptor 2A P28223 Details
5-hydroxytryptamine receptor 2B P41595 Details
5-hydroxytryptamine receptor 2C P28335 Details
5-hydroxytryptamine receptor 3A P46098 Details
5-hydroxytryptamine receptor 3B O95264 Details
5-hydroxytryptamine receptor 3C Q8WXA8 Details
5-hydroxytryptamine receptor 3D Q70Z44 Details
5-hydroxytryptamine receptor 3E A5X5Y0 Details
5-hydroxytryptamine receptor 4 Q13639 Details
5-hydroxytryptamine receptor 6 P50406 Details
5-hydroxytryptamine receptor 7 P34969 Details

References:

  1. Flynn BL, Ranno AE: Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives. Ann Pharmacother. 1999 Feb;33(2):188-97. Pubmed
  2. Markstein R: Hydergine: interaction with the neurotransmitter systems in the central nervous system. J Pharmacol. 1985;16 Suppl 3:1-17. Pubmed
  3. Wadworth AN, Chrisp P: Co-dergocrine mesylate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in age-related cognitive decline. Drugs Aging. 1992 May-Jun;2(3):153-73. Pubmed
  4. Korneyev AY, Cincotta AH: Identification of hepatic, non-monoamine, dihydroergocryptine binding sites with significant gender differences. Life Sci. 1996;58(12):241-8. Pubmed

5. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist agonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

References:

  1. Flynn BL, Ranno AE: Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives. Ann Pharmacother. 1999 Feb;33(2):188-97. Pubmed
  2. Markstein R: Hydergine: interaction with the neurotransmitter systems in the central nervous system. J Pharmacol. 1985;16 Suppl 3:1-17. Pubmed
  3. Wadworth AN, Chrisp P: Co-dergocrine mesylate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in age-related cognitive decline. Drugs Aging. 1992 May-Jun;2(3):153-73. Pubmed
  4. Korneyev AY, Cincotta AH: Identification of hepatic, non-monoamine, dihydroergocryptine binding sites with significant gender differences. Life Sci. 1996;58(12):241-8. Pubmed

6. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist agonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

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

7. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. Tvrdeic A, Pericic D: Effect of ergot alkaloids on 3H-flunitrazepam binding to mouse brain GABAA receptors. Coll Antropol. 2003;27 Suppl 1:175-82. Pubmed
  2. Tvrdeic A, Pericic D: Dihydrogenated ergot compounds bind with high affinity to GABAA receptor-associated Cl- ionophore. Eur J Pharmacol. 1991 Sep 4;202(1):109-11. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

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Drug created on June 13, 2005 07:24 / Updated on January 17, 2014 13:56