Identification
- Summary
Ergoloid mesylate is a nootropic with an unknown mechanism of action indicated in individuals over sixty who manifest signs and symptoms of an idiopathic decline in mental capacity.
- Brand Names
- Hydergine
- Generic Name
- Ergoloid mesylate
- DrugBank Accession Number
- DB01049
- Background
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.10Later in 1991, the mixture of ergoloid mesylates was retaken by Sun Pharmaceutical Industries and approved by the FDA.11 To know more about the individual components of the ergoloid mixture, please visit Epicriptine, Dihydro-alpha-ergocryptine, Dihydroergocornine and Dihydroergocristine.
- Type
- Small Molecule
- Groups
- Approved
- Synonyms
- co-dergocrine mesilate
- co-dergocrine mesylate
- co-dergocrine methanesulfonate
- codergocrine mesilate
- codergocrine mesylate
- codergocrine methanesulfonate
- Dihydroergotoxine Mesilate
- Dihydroergotoxine Mesylate
- Dihydroergotoxine Methanesulfonate
- dihydroergotoxine methanesulfonates
- dihydroergotoxine monomethanesulfonate
- dihydrogenated ergot alkaloids
- Ergoloid Mesilates
- Ergoloid Mesylates
- ergoloid methanesulfonate
- ergoloid methanesulfonates
- hydrogenated ergot alkaloids
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 condition2 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.12 To know more about the individual components of the ergoloid mixture, please visit Dihydroergocristine and Dihydro-alpha-ergocryptine
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Mental capacity decline •••••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ADopamine receptor antagonistagonistHumans AAlpha adrenergic receptor antagonistagonistHumans ABeta adrenergic receptor antagonistagonistHumans ASerotonin Receptors antagonistagonistHumans - 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.14 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 CYP3A4.13 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.9 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.
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Ergoloid mesylate is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Ergoloid mesylate can be increased when it is combined with Abametapir. Acebutolol Acebutolol may increase the vasoconstricting activities of Ergoloid mesylate. Aceclofenac The risk or severity of hypertension can be increased when Ergoloid mesylate is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Ergoloid mesylate is combined with Acemetacin. - Food Interactions
- Take with or without food. Taking ergoloid mesylate with food may reduce gastrointestinal upset.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Alkergot (Eon Labs) / Circanol (3M) / Deapril (Bristol Myers Squibb) / Gerimal
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Hydergine Tablet 1 mg/1 Oral Novartis 1983-01-18 2008-09-09 US 
Hydergine Liquid 1 mg/1mL Oral Novartis 1983-01-18 2008-09-09 US Hydergine LC Capsule, liquid filled 1 mg/1 Oral Novartis 1983-01-18 2008-09-09 US Hydergine Tablets, 1mg Tablet 1 mg Oral Sterimax Inc 1968-12-31 Not applicable Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image TOTERJİN DAMLA, 50 CC Ergoloid mesylate (33 %) + Dihydroergocristine (33 %) + Dihydroergocryptine (33 %) Solution / drops Oral BİLİM İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 2018-08-16 Turkey 
Categories
- Drug Categories
- Adrenergic Agents
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Alkaloids
- Antidepressive Agents
- Cardiovascular Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Dihydroergotoxine
- Dopamine Agents
- Dopamine Agonists
- Ergot Alkaloids and Derivatives
- Ergot-derivative Dopamine Receptor Agonists
- Ergotamines
- Heterocyclic Compounds, Fused-Ring
- Neurotransmitter Agents
- Nootropic Agents
- Peripheral Vasodilators
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Sympatholytic (Adrenergic Blocking) Agents
- Vasodilating Agents
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- X3S33EX3KW
- CAS number
- 8067-24-1
References
- General References
- 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. [Article]
- Delagarza VW: New drugs for Alzheimer's disease. Am Fam Physician. 1998 Oct 1;58(5):1175-82. [Article]
- PERCHESON PB, CARROLL JJ: The use of hydergine in obstetrics. Can Med Assoc J. 1954 Dec;71(6):588-94. [Article]
- 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. [Article]
- Schran HF, McDonald S, Lehr R: Pharmacokinetics and bioavailability of ergoloid mesylates. Biopharm Drug Dispos. 1988 Jul-Aug;9(4):349-61. doi: 10.1002/bod.2510090404. [Article]
- Seyffart G. (1992). Drug dosage in renal insufficiency (2nd ed.). Springer Science+Business Media Dordrecht.
- Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
- Barceloux D. (2008). Medical toxicology of natural substances. Wiley. [ISBN:978-0-470-33447-4]
- Berde B. and Schild H. (1978). Ergot alkaloids and related compounds. Springer-Verlag. [ISBN:978-3-642-66777-0]
- FDA approval [Link]
- FDA approval [Link]
- Dailymed [Link]
- Kegg [Link]
- Pharmacopeia [File]
- External Links
- MSDS
- Download (47.2 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment Fragile X Syndrome 1 2 Completed Treatment Vascular Dementia (VaD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Gallipot
- Prescript Pharmaceuticals
- Dosage Forms
Form Route Strength Solution Oral 1 mg Solution / drops Oral Tablet Oral Tablet Oral 4.5 mg Solution Oral 0.00106 g Liquid Oral 1 mg/1mL Tablet Oral 1 mg/1 Capsule, liquid filled Oral 1 mg/1 Solution / drops Oral 1 mg/ml Solution / drops Oral Tablet Oral 1 mg Tablet Oral 1.5 mg - Prices
Unit description Cost Unit Ergoloid mesylates powder 87.5USD g Ergoloid mesylates 1 mg tablet 1.3USD tablet Hydergine 1 mg Tablet 1.1USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 192 ºC 'MSDS' boiling point (°C) Decomposes 'MSDS' water solubility Partially soluble 'MSDS' logP 2.8 HMDB - Predicted Properties
- Not Available
- 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 inhibitor Non-inhibitor 0.7072 CYP450 2D6 inhibitor Non-inhibitor 0.9221 CYP450 2C19 inhibitor Non-inhibitor 0.6493 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- General Function
- G-protein coupled amine receptor activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Components:
| Name | UniProt ID |
|---|---|
| D(1A) dopamine receptor | P21728 |
| D(1B) dopamine receptor | P21918 |
| D(2) dopamine receptor | P14416 |
| D(3) dopamine receptor | P35462 |
| D(4) dopamine receptor | P21917 |
References
- Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- 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
- Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- 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:
| Name | UniProt ID |
|---|---|
| Beta-1 adrenergic receptor | P08588 |
| Beta-2 adrenergic receptor | P07550 |
| Beta-3 adrenergic receptor | P13945 |
References
- Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- 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
- Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
- Kegg [Link]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54