Identification

Name
Dihydroergocornine
Accession Number
DB11273
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • 9,10-dihydroergocornine
Product Ingredients
IngredientUNIICASInChI Key
Dihydroergocornine mesylate42RX8KPW2929261-94-7UOOWRCRLTSXSAV-GSZJWLEYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ergoloid MesylatesDihydroergocornine 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)TabletOralCarilion Materials Management1991-10-31Not applicableUs
Ergoloid MesylatesDihydroergocornine 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)TabletOralPhysicians Total Care, Inc.1991-10-312012-10-08Us
Ergoloid MesylatesDihydroergocornine 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)TabletOralAv Kare, Inc.2014-08-222015-09-15Us
Ergoloid MesylatesDihydroergocornine 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)TabletOralSun Pharmaceutical Industries Limited1991-10-31Not applicableUs
Ergoloid MesylatesDihydroergocornine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.333 mg/1) + Dihydroergocristine mesylate (0.333 mg/1)Tablet, orally disintegratingOralIVAX Pharmaceuticals, Inc.1980-11-202008-09-30Us
Categories
UNII
IK4C1OC8NE
CAS number
25447-65-8
Weight
Average: 563.699
Monoisotopic: 563.31076944
Chemical Formula
C31H41N5O5
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

Pharmacology

Indication

To know more about the approved indications please visit Ergoloid mesylate

Associated Conditions
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]

TargetActionsOrganism
ASerotonin Receptors
antagonist
agonist
Human
ABeta adrenergic receptor
antagonist
agonist
Human
AAlpha adrenergic receptor
antagonist
agonist
Human
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.

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.

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

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineDihydroergocornine may increase the hypertensive activities of 4-Methoxyamphetamine.
AcebutololAcebutolol may increase the vasoconstricting activities of Dihydroergocornine.
AcetazolamideThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Acetazolamide.
Acetyl sulfisoxazoleThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Acetyl sulfisoxazole.
AgmatineDihydroergocornine may increase the hypertensive and vasoconstricting activities of Agmatine.
AlclometasoneThe metabolism of Dihydroergocornine can be decreased when combined with Alclometasone.
AlfuzosinThe metabolism of Dihydroergocornine can be decreased when combined with Alfuzosin.
AmbroxolThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Ambroxol.
AmcinonideThe metabolism of Dihydroergocornine can be decreased when combined with Amcinonide.
AmiodaroneThe metabolism of Dihydroergocornine can be decreased when combined with Amiodarone.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:15415441]
  2. 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. [PubMed:15395942]
  3. Bercel NA: TREATMENT OF MIGRAINE-Results with Dihydroergocornine Methanesulfonate (DHO-180) and Other Ergot Derivatives. Calif Med. 1950 Apr;72(4):234-8. [PubMed:18731688]
  4. 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. [PubMed:16695718]
  5. 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. [PubMed:18152249]
  6. 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. [PubMed:7063048]
  7. Florey K. (1978). Analytical profiles of drug substances (7th ed.). Academic Press. [ISBN:0-12-260807-0]
  8. Berde B. and Schild H. (1978). Ergot alkaloids and related compounds. Springer-Verlag. [ISBN:978-3-642-66777-0]
  9. Barceloux D. (2008). Medical toxicology of natural substances. Wiley. [ISBN:978-0-470-33447-4]
  10. Preston S. (1917). Endocrinology. Williams & Wilkins Co..
External Links
ChemSpider
147720
ChEBI
59909
ChEMBL
CHEMBL2365712
Wikipedia
Dihydroergocornine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, orally disintegratingOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)187 ºCFlorey K. Analytical profiles of drug substances. 1978.
boiling point (°C)DecomposesFlorey K. Analytical profiles of drug substances. 1978.
logP2.33ChemSrc
Predicted Properties
PropertyValueSource
Water Solubility0.402 mg/mLALOGPS
logP3.1ALOGPS
logP3.06ChemAxon
logS-3.2ALOGPS
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 Count4ChemAxon
Refractivity152.66 m3·mol-1ChemAxon
Polarizability62 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Ergopeptine / Hybrid peptide / Alpha-dipeptide / Lysergic acid amide / Indoloquinoline / Benzoquinoline / Quinoline-3-carboxamide / N-acyl-alpha amino acid or derivatives / Pyrroloquinoline / Alpha-amino acid or derivatives
show 41 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
ergot alkaloid (CHEBI:59909)

Targets

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. 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. [PubMed:7063048]
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. 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. [PubMed:7063048]
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. 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. [PubMed:7063048]

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

Drug created on December 03, 2015 09:51 / Updated on September 07, 2018 03:26