Identification

Name
Ergoloid mesylate
Accession Number
DB01049  (APRD00711, DB01287)
Type
Small Molecule
Groups
Approved
Description

Ergoloid Mesylate is an equiproportional preparation of three different ergotamantriones: dihydroergocornine, dihydroergocristine, and dihydroergocryptine.[1] All these components are produced by the fungus Claviceps purpurea and are all derivatives of the tetracyclic compound 6-methylergonovine.[7] The derivatives of this fungus are identified to be about 350 different substances from which the components of the ergoloid mesylate mixture are composed of the dihydrogenated ergot alkaloid derivatives.[3] The mixture of ergoloid mesylate was first developed by Novartis and FDA approved on November 5, 1953, but this specific formulation is now discontinued.[9]Later in 1991, the mixture of ergoloid mesylates was retaken by Sun Pharmaceutical Industries and approved by the FDA.[10] To know more about the individual components of the ergoloid mixture, please visit Epicriptine, Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

Synonyms
  • co-dergocrine mesilate
  • co-dergocrine mesylate
  • co-dergocrine methanesulfonate
  • codergocrine mesilate
  • codergocrine mesylate
  • codergocrine methanesulfonate
  • Dihydroergotoxine Mesilate
  • Dihydroergotoxine Mesylate
  • dihydroergotoxine methanesulfonate
  • Dihydroergotoxine Methanesulfonate
  • dihydroergotoxine methanesulfonates
  • dihydroergotoxine monomethanesulfonate
  • dihydrogenated ergot alkaloids
  • Ergoloid Mesilates
  • Ergoloid Mesylates
  • ergoloid methanesulfonate
  • ergoloid methanesulfonates
  • hydrogenated ergot alkaloids
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HydergineLiquid1 mg/1mLOralNovartis1983-01-182008-09-09Us
HydergineTablet1 mg/1OralNovartis1983-01-182008-09-09Us
Hydergine LCCapsule, liquid filled1 mg/1OralNovartis1983-01-182008-09-09Us
Hydergine Tablets, 1mgTablet1 mgOralSterimax Inc1968-12-31Not applicableCanada
International/Other Brands
Alkergot (Eon Labs) / Circanol (3M) / Deapril (Bristol Myers Squibb) / Gerimal / Hydergine (Novartis)
Categories
UNII
X3S33EX3KW
CAS number
8067-24-1
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

It was labeled by the FDA for the treatment of symptoms of an idiopathic decline in the mental capacity not related to a potentially reversible condition[2] as well as for age-related cognitive impairment.[4] The prescription of this drug is conditioned to the corroboration that the patient is not suffering from a potentially reversible and treatable condition especially delirium and dementiform illness secondary to systemic disease, primary neurological disease or primary mood disturbance.[11] To know more about the individual components of the ergoloid mixture, please visit Dihydroergocristine and Dihydro-alpha-ergocryptine

Associated Conditions
Pharmacodynamics

The mechanism of action of ergoloid mesylate is not completely established but it is thought that it increases both the blood flow and cerebral metabolism. Some studies have shown a significant improvement in alertness and memory, as well as a decline in confusion while some other benefits have shown a lack of effect.[2] Its action produces a damper in the impulses from the vasomotor center which reduces the vascular tone which translates in the slow of pulse rate, prevention of compensatory tachycardia.[3] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

Mechanism of action

The general mechanism of action of ergoloid mesylate is the dual action of partial agonism/antagonism of adrenergic, dopaminergic and serotonergic receptors. The pharmacological activity is determined by the degree of activity of each component at the receptor site.[7] To know more about the individual components of the ergoloid mixture, please visit Epicriptine, Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

TargetActionsOrganism
ADopamine receptor
antagonist
agonist
Human
AAlpha adrenergic receptor
antagonist
agonist
Human
ABeta adrenergic receptor
antagonist
agonist
Human
ASerotonin Receptors
antagonist
agonist
Human
Absorption

The maximal plasma concentration of the components of the mixture of ergoloid mesylates is approximately 0.04 mcg/l. The analysis of the concentration of the major metabolites of each component indicates that all ergoloid mesylate are rapidly transformed after absorption. This finding is supported as they were found in one order of magnitude higher in concentration when compared to the original form.[3] Ergoloid mesylate seems to have a very low absorption of only 25%. From this absorption by the GI tract, approximately 50% of the absorbed dose is eliminated by first-pass metabolism. After absorption, the maximal plasma concentration is attained after 3-4 hours and the oral bioavailability is very low.[6] Simultaneous food ingestion has no effect on the extent of absorption but it does lower the absorption rate.[5] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

Volume of distribution

The volume of distribution is about 2 L/kg.[7] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine and Dihydroergocristine.

Protein binding

Ergoloid mesylate presents a very large plasma protein binding that accounts for 81% of the administered dose.[13] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine and Dihydroergocristine.

Metabolism

Most of the metabolism of ergoloid mesylate is hepatic and it is performed very rapidly after absorption. After exposition in vitro, the major metabolites identified are hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine.[4] All metabolic transformations seem to be related to the activity of the cytochrome CYP3A4.[12] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

Route of elimination

The ergoloid mesylate mixture is mainly excreted via bile in feces. The ratio of the eliminated dose via urine after intravenous and oral administration is 8.4% and 2% respectively.[6] Urinary excretion of the unchanged drug is very small and bile excretion is represented mainly by ergot metabolites conformed as conjugated compounds.[T191] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

Half life

The reported plasma half-life of ergoloid mesylate is 3.5 hours while the terminal half-life is of 13 hours.[6] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine.

Clearance

To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine and Dihydroergocristine.

Toxicity

Symptoms of overdose include dyspnea, hypotension or hypertension, rapid weak pulse, delirium, nausea, vomiting, and bradycardia. The excessive use of ergoloid mesylate can lead to ergotism.[7] To know more about the individual components of the ergoloid mixture, please visit Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe serum concentration of Ergoloid mesylate can be increased when it is combined with (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE.
1,10-PhenanthrolineThe serum concentration of Ergoloid mesylate can be increased when it is combined with 1,10-Phenanthroline.
3,4-DichloroisocoumarinThe serum concentration of Ergoloid mesylate can be increased when it is combined with 3,4-Dichloroisocoumarin.
4-(2-Aminoethyl)Benzenesulfonyl FluorideThe serum concentration of Ergoloid mesylate can be increased when it is combined with 4-(2-Aminoethyl)Benzenesulfonyl Fluoride.
4-MethoxyamphetamineErgoloid mesylate may increase the hypertensive and vasoconstricting activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineErgoloid mesylate may increase the vasoconstricting activities of 5-methoxy-N,N-dimethyltryptamine.
AcebutololAcebutolol may increase the vasoconstricting activities of Ergoloid mesylate.
AcepromazineThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Aceprometazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Acetophenazine.
Food Interactions
Not Available

References

General References
  1. Thompson TL 2nd, Filley CM, Mitchell WD, Culig KM, LoVerde M, Byyny RL: Lack of efficacy of hydergine in patients with Alzheimer's disease. N Engl J Med. 1990 Aug 16;323(7):445-8. doi: 10.1056/NEJM199008163230704. [PubMed:2082953]
  2. Delagarza VW: New drugs for Alzheimer's disease. Am Fam Physician. 1998 Oct 1;58(5):1175-82. [PubMed:9787282]
  3. PERCHESON PB, CARROLL JJ: The use of hydergine in obstetrics. Can Med Assoc J. 1954 Dec;71(6):588-94. [PubMed:13209453]
  4. Bicalho B, Giolo JM, Lilla S, De Nucci G: Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results. Biopharm Drug Dispos. 2008 Jan;29(1):17-28. doi: 10.1002/bdd.585. [PubMed:17941060]
  5. Schran HF, McDonald S, Lehr R: Pharmacokinetics and bioavailability of ergoloid mesylates. Biopharm Drug Dispos. 1988 Jul-Aug;9(4):349-61. [PubMed:3207855]
  6. Seyffart G. (1992). Drug dosage in renal insufficiency (2nd ed.). Springer Science+Business Media Dordrecht.
  7. Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
  8. Barceloux D. (2008). Medical toxicology of natural substances. Wiley. [ISBN:978-0-470-33447-4]
  9. FDA approval [Link]
  10. FDA approval [Link]
  11. Dailymed [Link]
  12. Kegg [Link]
  13. Pharmacopeia [File]
External Links
KEGG Drug
D02268
KEGG Compound
C14055
PubChem Substance
46505963
ChemSpider
60600935
ChEBI
34706
Therapeutic Targets Database
DAP000901
PharmGKB
PA164752439
Wikipedia
Ergoloid
AHFS Codes
  • 12:16.00 — Sympatholytic (Adrenergic Blocking) Agents
MSDS
Download (47.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentDementia, Vascular1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Gallipot
  • Prescript Pharmaceuticals
Dosage forms
FormRouteStrength
LiquidOral1 mg/1mL
TabletOral1 mg/1
Capsule, liquid filledOral1 mg/1
TabletOral1 mg
Prices
Unit descriptionCostUnit
Ergoloid mesylates powder87.5USD g
Ergoloid mesylates 1 mg tablet1.3USD tablet
Hydergine 1 mg Tablet1.1USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)192 ºC'MSDS'
boiling point (°C)Decomposes'MSDS'
water solubilityPartially soluble'MSDS'
logP2.8HMDB
Predicted Properties
Not Available
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8284
Blood Brain Barrier-0.9494
Caco-2 permeable-0.6447
P-glycoprotein substrateSubstrate0.6838
P-glycoprotein inhibitor IInhibitor0.6581
P-glycoprotein inhibitor IINon-inhibitor0.8001
Renal organic cation transporterNon-inhibitor0.8838
CYP450 2C9 substrateNon-substrate0.75
CYP450 2D6 substrateNon-substrate0.7966
CYP450 3A4 substrateSubstrate0.6681
CYP450 1A2 substrateNon-inhibitor0.7702
CYP450 2C9 inhibitorNon-inhibitor0.7072
CYP450 2D6 inhibitorNon-inhibitor0.9221
CYP450 2C19 inhibitorNon-inhibitor0.6493
CYP450 3A4 inhibitorNon-inhibitor0.7973
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8464
Ames testNon AMES toxic0.6324
CarcinogenicityNon-carcinogens0.6535
BiodegradationNot ready biodegradable0.9321
Rat acute toxicity2.5438 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8821
hERG inhibition (predictor II)Inhibitor0.5783
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

Components:
References
  1. Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Protein heterodimerization activity
Specific Function
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) prot...

Components:
References
  1. Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...

Components:
References
  1. Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...

Components:
References
  1. Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kegg [Link]

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 00:08