Identification
- Summary
Dihydroergocornine 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.
- Generic Name
- Dihydroergocornine
- DrugBank Accession Number
- DB11273
- Background
Dihydroergocornine is one of the dihydrogenated ergot compounds that present very large hypotensive effects.1 It is an artificial derivative of the crude extract of ergot and later purified, ergocornine.2 The formation of dihydroergocornine implies the hydrogenation of the double bonds in the lysergic acid.3 Dihydroergocornine presents a formula of 9,10 alpha-dihydro-12'-hydroxy-2',5'alpha-bis(1-methylethyl)-ergotaman-3',6',18-trione.7 It is found as one of the components in the ergoloid mesylate mixture. To know more about this mixture please refer to Ergoloid mesylate
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Dihydroergocornine (DB11273)
- Weight
- Average: 563.699
Monoisotopic: 563.31076944 - Chemical Formula
- C31H41N5O5
- Synonyms
- 9,10-dihydroergocornine
- Dihydroergocornine
Pharmacology
- Indication
To know more about the approved indications please visit Ergoloid mesylate
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for symptomatic treatment of No primary neurologial disease, idiopathic decreased mental activity Combination Product in combination with: Dihydroergocristine (DB13345), Dihydro-alpha-ergocryptine (DB11274) •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
It is reported that dihydroergocornine administration, in non-toxic doses, presents sympatholytic and hypotensive properties which are observed as a significantly decreased mean arterial pressure.2 In the brain, the activity of dihydroergocornine was observed as a decrease in cerebral blood flow, cerebral vascular resistance and oxygen uptake. The effect in the brain seems to allow a cerebral metabolic homeostasis.1 To know more about the pharmacology please visit Ergoloid mesylate
- Mechanism of action
The mechanism of action by which dihydroergocornine exerts its effects are not entirely defined. However, it is reported that dihydroergocornine has central and peripheral effects. The fall in blood pressure seems to be related to the stimulation of the vasodilator center.4 It has been demonstrated that dihydroergocornine possesses potent adrenolytic and sympathicolytic actions.5 The effect of dihydroergocornine is related to the inhibitory effect against the serotonin and noradrenaline receptors in which dihydroergocornine seems to be very potent against a stimulation-induced noradrenaline overflow. It also presents a stimulatory effect in arterial and venous smooth muscle when administered at slightly higher concentrations than the necessary for the inhibitory effect.6
Target Actions Organism ASerotonin Receptors antagonistagonistHumans ABeta adrenergic receptor antagonistagonistHumans AAlpha adrenergic receptor antagonistagonistHumans - Absorption
Dihydroergocornine absorption in man after oral administration is very rapid when compared to the mixture or most of the components. The time to reach maximum plasma concentration or 0.57 ng-eq/ml is 1.4 hours. It presents an absorption half-life of 0.32 hours. The absorption percentage is of about 25% which corresponds to the registered absorption presented in the ergoloid mixture.8 To know more about the pharmacokinetics please visit Ergoloid mesylate.
- Volume of distribution
To know more about the pharmacokinetics please visit Ergoloid mesylate.
- Protein binding
To know more about the pharmacokinetics please visit Ergoloid mesylate.
- Metabolism
The biotransformation of dihydroergocornine occurs via oxidation and cleavage of the proline in the peptide portion of the molecule as well as by the splitting of the amide bond yielding dihydrolysergic acid amide. Some of the derivate metabolites retain the essential ring structure of the ergot alkaloid.9 To know more about the pharmacokinetics please visit Ergoloid mesylate.
- Route of elimination
When orally administered, dihydroergocornine is almost completely eliminated via feces. The urinary secretion accounts only for 2.5% of the administered dose. On the other hand, when administered intravenously, the renal excretion can account for approximately 10% of the administered dose.8 To know more about the pharmacokinetics please visit Ergoloid mesylate.
- Half-life
To know more about the pharmacokinetics please visit Ergoloid mesylate.
- Clearance
No pharmacokinetic related to the clearance rate was found in current literature.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Dihydroergocornine effect on fertility was tested in preclinical studies. The reported effect was a decreased weight gain in neonates.10 Overdosing has also been reported to present effects of fall of blood pressure and a decrease in heart rate to 13 beats per minute.4 To know more about the pharmacokinetics please visit Ergoloid mesylate.
- 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 softwareAbametapir The serum concentration of Dihydroergocornine can be increased when it is combined with Abametapir. Abatacept The metabolism of Dihydroergocornine can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Dihydroergocornine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Dihydroergocornine. Acebutolol Acebutolol may increase the vasoconstricting activities of Dihydroergocornine. - Food Interactions
- No interactions found.
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.- Product Ingredients
Ingredient UNII CAS InChI Key Dihydroergocornine mesylate 42RX8KPW29 29261-94-7 UOOWRCRLTSXSAV-GSZJWLEYSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ergoloid Mesylates Dihydroergocornine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocristine mesylate (0.333 mg/1) + Epicriptine mesilate (0.111 mg/1) Tablet Oral Av Kare, Inc. 2014-08-22 2015-09-15 US 
Ergoloid Mesylates Dihydroergocornine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocristine mesylate (0.333 mg/1) + Epicriptine mesilate (0.111 mg/1) Tablet Oral Sun Pharmaceutical Industries Limited 1991-10-31 Not applicable US Ergoloid Mesylates Dihydroergocornine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.333 mg/1) + Dihydroergocristine mesylate (0.333 mg/1) Tablet, orally disintegrating Oral IVAX Pharmaceuticals, Inc. 1980-11-20 2008-09-30 US Ergoloid Mesylates Dihydroergocornine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocristine mesylate (0.333 mg/1) + Epicriptine mesilate (0.111 mg/1) Tablet Oral Carilion Materials Management 1991-10-31 Not applicable US Ergoloid Mesylates Dihydroergocornine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocristine mesylate (0.333 mg/1) + Epicriptine mesilate (0.111 mg/1) Tablet Oral Physicians Total Care, Inc. 1991-10-31 2012-10-08 US
Categories
- Drug Categories
- Agents that produce hypertension
- Alkaloids
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Dopamine Agents
- Dopamine Agonists
- Ergot Alkaloids and Derivatives
- Ergot-derivative Dopamine Receptor Agonists
- Ergotamines
- Heterocyclic Compounds, Fused-Ring
- Neurotransmitter Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as ergopeptines. These are ergoline derivatives that contain a tripeptide structure attached to the basic ergoline ring in the same location as the amide group of the lysergic acid derivatives.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Ergoline and derivatives
- Sub Class
- Lysergic acids and derivatives
- Direct Parent
- Ergopeptines
- Alternative Parents
- Hybrid peptides / Dipeptides / Lysergamides / Indoloquinolines / Benzoquinolines / Quinoline-3-carboxamides / Pyrroloquinolines / N-acyl-alpha amino acids and derivatives / 3-alkylindoles / Piperidinecarboxamides show 20 more
- Substituents
- 1,4-diazinane / 3-alkylindole / 3-piperidinecarboxamide / Alkanolamine / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound show 41 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- ergot alkaloid (CHEBI:59909)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- IK4C1OC8NE
- CAS number
- 25447-65-8
- InChI Key
- SEALOBQTUQIVGU-QNIJNHAOSA-N
- InChI
- InChI=1S/C31H41N5O5/c1-16(2)26-28(38)35-11-7-10-24(35)31(40)36(26)29(39)30(41-31,17(3)4)33-27(37)19-12-21-20-8-6-9-22-25(20)18(14-32-22)13-23(21)34(5)15-19/h6,8-9,14,16-17,19,21,23-24,26,32,40H,7,10-13,15H2,1-5H3,(H,33,37)/t19-,21-,23-,24+,26+,30-,31+/m1/s1
- IUPAC Name
- (2R,4R,7R)-N-[(1S,2S,4R,7S)-2-hydroxy-5,8-dioxo-4,7-bis(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
- SMILES
- [H][C@@]12CCCN1C(=O)[C@H](C(C)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
References
- General References
- HAFKENSCHIEL JH, CRUMPTON CW, MOYER JH, JEFFERS WA, FISHEL HANLEY B, CONLIN HARNED S: The effects of dihydroergocornine on the cerebral circulation of patients with essential hypertension. J Clin Invest. 1950 Apr;29(4):408-11. doi: 10.1172/JCI102273. [Article]
- FREIS ED, STANTON JR, et al.: The hemodynamic effects of hypotensive drugs in man; dihydroergocornine. J Clin Invest. 1949 Nov;28(6 Pt 2):1387-1402. doi: 10.1172/JCI102204. [Article]
- Bercel NA: TREATMENT OF MIGRAINE-Results with Dihydroergocornine Methanesulfonate (DHO-180) and Other Ergot Derivatives. Calif Med. 1950 Apr;72(4):234-8. [Article]
- Hayes DW, Wakim KG, Horton BT, Peters GA: THE EFFECTS OF DIHYDROERGOCORNINE ON THE CIRCULATION IN THE EXTREMITIES OF MAN. J Clin Invest. 1949 Jul;28(4):615-20. doi: 10.1172/JCI102111. [Article]
- FLORMAN AL, FISCHER AE, MOLOSHOK RE: An evaluation of the mumps skin-test in pediatric practice. Bull N Y Acad Med. 1949 Jul;25(7):441. [Article]
- Muller-Schweinitzer E: Actions of co-dergocrine mesylate and its components at vascular smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):225-33. [Article]
- Florey K. (1978). Analytical profiles of drug substances (7th ed.). Academic Press. [ISBN:0-12-260807-0]
- Berde B. and Schild H. (1978). Ergot alkaloids and related compounds. Springer-Verlag. [ISBN:978-3-642-66777-0]
- Barceloux D. (2008). Medical toxicology of natural substances. Wiley. [ISBN:978-0-470-33447-4]
- Preston S. (1917). Endocrinology. Williams & Wilkins Co..
- External Links
- ChemSpider
- 147720
- 3415
- ChEBI
- 59909
- ChEMBL
- CHEMBL2365712
- ZINC
- ZINC000004215648
- Wikipedia
- Dihydroergocornine
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
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, orally disintegrating Oral Tablet - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 187 ºC Florey K. Analytical profiles of drug substances. 1978. boiling point (°C) Decomposes Florey K. Analytical profiles of drug substances. 1978. logP 2.33 ChemSrc - Predicted Properties
Property Value Source Water Solubility 0.402 mg/mL ALOGPS logP 3.1 ALOGPS logP 3.06 Chemaxon logS -3.2 ALOGPS 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 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 152.66 m3·mol-1 Chemaxon Polarizability 62 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 241.4336497 predictedDarkChem Lite v0.1.0 [M-H]- 226.68616 predictedDeepCCS 1.0 (2019) [M+H]+ 239.2339497 predictedDarkChem Lite v0.1.0 [M+H]+ 228.58156 predictedDeepCCS 1.0 (2019) [M+Na]+ 238.8820497 predictedDarkChem Lite v0.1.0 [M+Na]+ 234.6534 predictedDeepCCS 1.0 (2019)
Targets
- 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
- Muller-Schweinitzer E: Actions of co-dergocrine mesylate and its components at vascular smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):225-33. [Article]
- 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
- Muller-Schweinitzer E: Actions of co-dergocrine mesylate and its components at vascular smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):225-33. [Article]
- 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
- Muller-Schweinitzer E: Actions of co-dergocrine mesylate and its components at vascular smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):225-33. [Article]
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
- Wooltorton E: Risk of stroke, gangrene from ergot drug interactions. CMAJ. 2003 Apr 15;168(8):1015. [Article]
Drug created at December 03, 2015 16:51 / Updated at January 16, 2021 21:46