Identification
- Summary
Dihydroergocristine is an ergot alkaloid used to delay progressive mental decline in conditions like Alzheimer's.
- Generic Name
- Dihydroergocristine
- DrugBank Accession Number
- DB13345
- Background
Dihydroergocristine is part of the ergoloid mixture products.7 It is a semisynthetic ergot alkaloid and thus, it is characterized by a structural skeleton formed by an alkaloid ergoline.1 To know more about ergoloid mixtures, please visit Ergoloid mesylate.
- Type
- Small Molecule
- Groups
- Approved, Experimental
- Structure
Structure for Dihydroergocristine (DB13345)
- Weight
- Average: 611.743
Monoisotopic: 611.31076944 - Chemical Formula
- C35H41N5O5
- Synonyms
- 9,10-dihydroergocristine
- DHEC
- External IDs
- GNF-Pf-3462
Pharmacology
- Indication
Dihydroergocristine is used in some countries such as Brasil as a single agent for the treatment of cerebral and peripheric vascular events.8 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, 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 Symptomatic treatment of Cerebrovascular diseases •••••••••••• ••••••• Management of Cognitive function •••••••••••• ••••••• ••••••• Treatment of Reduction of blood flow •••••••••••• ••••••• Symptomatic treatment of Vascular diseases of the extremities •••••••••••• ••••••• Used in combination to manage Vascular disorders Combination Product in combination with: Dihydroergocornine (DB11273), Dihydroergocryptine (DB13385) •••••••••••• •••••• ••••••• •••••• - Contraindications & Blackbox Warnings
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Dihydroergocristine has been shown to present effect on memory and cognition. This activity in the brain is been reported by an increase in glutathione in age-related brain states.2 The reported effect on serotonin and adrenergic receptors has also been correlated to an inhibition of platelet aggregation.8 It has also been reported that individuals exposed to dihydroergocristine may present an amphoteric vasoregulating activity either hypotensive in hypertensive individuals or hypertensive in hypotensive individuals.1 This action is performed by promoting a dilating action in the contracted arteries and a tonic action in the dilated arteries and arterioles.8 The vasoregulating effect causes an increase in cerebral blood flow and oxygen consumption by the brain, which correlates with the brain protective function of dihydroergocristine.2 In Alzheimer studies, dihydroergocristine reduced the amyloid-beta levels in different cell types.4 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
- Mechanism of action
Dihydroergocristine mechanism of action seems to be related to a noncompetitive antagonistic activity in the serotonin receptors as well as a double partial agonist/antagonist activity in dopaminergic and adrenergic receptors.2 In Alzheimer studies, dihydroergocristine act as a direct inhibitor of γ-secretase.4
Target Actions Organism ASerotonin Receptors antagonistHumans ABeta adrenergic receptor antagonistagonistHumans AAlpha adrenergic receptor antagonistagonistHumans ADopamine receptor antagonistagonistHumans - Absorption
Dihydroergocristine presents an absorption in the digestive tract of about 25% of the administered dose. When dihydroergocristine was orally administered in humans and the peak plasma concentration of 0.28 mcg/l was achieved after 0.46 hours. In the same report, the AUC was reported to be 0.39 mcg/l.h.3 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
- Volume of distribution
Dihydroergocristine presents a large volume of distribution of 52 l/kg.6 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
- Protein binding
Dihydroergocristine can be found in a bound state to plasma proteins in a proportion of even 68% of the administered dose.3 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
- Metabolism
The major metabolite of dihydroergocristine is 8'-hydroxy-dihydroergocristine is produced in the liver.3 The modification of dihydroergocristine in the body is very extensive and it has been observed as an almost complete absence of the unchanged drug.6 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
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- Route of elimination
The most important elimination route of dihydroergocristine is in via the bile and it accounts for over 85% of the eliminated dose. Urine elimination accounts only for 5% of the administered dose.5 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
- Half-life
The half-life of dihydroergocristine has only been studied as part of the therapeutic mixture, please refer to Ergoloid mesylate.
- Clearance
Dihydroergocristine presents a high systemic clearance rate of 2.65 l/h.hg.6 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate.
- Adverse Effects
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Studies related to acute and chronic toxicity as well as teratogenesis and fertility has proven that dihydroergocristine is a non-toxic and very well tolerated drug.2 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, 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 Dihydroergocristine can be increased when it is combined with Abametapir. Abatacept The metabolism of Dihydroergocristine can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Dihydroergocristine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Dihydroergocristine. Acebutolol Acebutolol may increase the vasoconstricting activities of Dihydroergocristine. - 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 Dihydroergocristine mesylate DS7CL18UAM 24730-10-7 SPXACGZWWVIDGR-SPZWACKZSA-N - International/Other Brands
- Iskevert (Medley S/A)
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ergoloid Mesylates Dihydroergocristine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine 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 Dihydroergocristine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine 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 Dihydroergocristine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.333 mg/1) + Dihydroergocornine mesylate (0.333 mg/1) Tablet, orally disintegrating Oral IVAX Pharmaceuticals, Inc. 1980-11-20 2008-09-30 US Ergoloid Mesylates Dihydroergocristine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine mesylate (0.333 mg/1) + Epicriptine mesilate (0.111 mg/1) Tablet Oral Carilion Materials Management 1991-10-31 Not applicable US Ergoloid Mesylates Dihydroergocristine mesylate (0.333 mg/1) + Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine 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
- ATC Codes
- C04AE54 — Dihydroergocristine, combinations
- C04AE — Ergot alkaloids
- C04A — PERIPHERAL VASODILATORS
- C04 — PERIPHERAL VASODILATORS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- Adrenergic Agents
- Adrenergic Antagonists
- Agents that produce hypertension
- Alkaloids
- BSEP/ABCB11 Substrates
- Cardiovascular Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Ergot Alkaloids and Derivatives
- Ergotamines
- Heterocyclic Compounds, Fused-Ring
- Neurotransmitter Agents
- Peripheral Vasodilators
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Ergoline and derivatives
- Sub Class
- Lysergic acids and derivatives
- Direct Parent
- Lysergamides
- Alternative Parents
- Indoloquinolines / Benzoquinolines / Pyrroloquinolines / N-acyl-alpha amino acids and derivatives / 3-alkylindoles / Isoindoles and derivatives / Piperidinecarboxamides / Aralkylamines / N-alkylpiperazines / Benzene and substituted derivatives show 17 more
- Substituents
- 1,4-diazinane / 3-alkylindole / 3-piperidinecarboxamide / Alkanolamine / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle show 41 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- ergot alkaloid (CHEBI:59912)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 05D48LUM4Z
- CAS number
- 17479-19-5
- InChI Key
- DEQITUUQPICUMR-HJPBWRTMSA-N
- InChI
- InChI=1S/C35H41N5O5/c1-20(2)34(37-31(41)23-16-25-24-11-7-12-26-30(24)22(18-36-26)17-27(25)38(3)19-23)33(43)40-28(15-21-9-5-4-6-10-21)32(42)39-14-8-13-29(39)35(40,44)45-34/h4-7,9-12,18,20,23,25,27-29,36,44H,8,13-17,19H2,1-3H3,(H,37,41)/t23-,25-,27-,28+,29+,34-,35+/m1/s1
- IUPAC Name
- (2R,4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-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
- SMILES
- [H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)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
- Drago F, Valerio C, Scalisi B, D'Agata V, Scapagnini U: Dihydroergocristine and memory alterations of aged male rats. Pharmacol Biochem Behav. 1988 Aug;30(4):961-5. [Article]
- Coppi G: [Dihydroergocristine. A review of pharmacology and toxicology]. Arzneimittelforschung. 1992 Nov;42(11A):1381-90. [Article]
- Bicalho B, Guzzo GC, Lilla S, Dos Santos HO, Mendes GD, Caliendo G, Perissutti E, Aiello A, Luciano P, Santagada V, Pereira AS, De Nucci G: Pharmacokinetics of dihydroergocristine and its major metabolite 8'-hydroxy-dihydroergocristine in human plasma. Curr Drug Metab. 2005 Dec;6(6):519-29. [Article]
- Lei X, Yu J, Niu Q, Liu J, Fraering PC, Wu F: The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-beta peptides. Sci Rep. 2015 Nov 16;5:16541. doi: 10.1038/srep16541. [Article]
- Nimmerfall F, Rosenthaler J: Ergot alkaloids: hepatic distribution and estimation of absorption by measurement of total radioactivity in bile and urine. J Pharmacokinet Biopharm. 1976 Feb;4(1):57-66. [Article]
- Grognet JM, Riviere R, Istin M, Zanotti A, Coppi G: [The pharmacokinetics of dihydroergocristine after intravenous and oral administration in rats]. Arzneimittelforschung. 1992 Nov;42(11A):1394-6. [Article]
- Dailymed [Link]
- ANVISA [Link]
- External Links
- KEGG Drug
- D07834
- ChemSpider
- 96884
- BindingDB
- 50390992
- 3416
- ChEBI
- 59912
- ChEMBL
- CHEMBL601773
- ZINC
- ZINC000003995616
- Wikipedia
- Dihydroergocristine
- MSDS
- Download (76.2 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
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution / drops Capsule Tablet Oral Tablet, orally disintegrating Oral Solution Oral Solution / drops Oral Tablet Capsule 3 mg Tablet, sugar coated Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 213-215 ºC 'MSDS' boiling point (°C) 899.3 ºC at 760 mm Hg Product specifications water solubility 10 mg/ml 'MSDS' logP 5.86 Buckingham J. et al. Dictionary of Alkaloids. pKa 6.9 Lemke T. and Williams D. Foye's Principles of Medicinal Chemistry. - Predicted Properties
Property Value Source Water Solubility 0.141 mg/mL ALOGPS logP 3.56 ALOGPS logP 3.83 Chemaxon logS -3.6 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 5 Chemaxon Refractivity 168.28 m3·mol-1 Chemaxon Polarizability 67.27 Å3 Chemaxon Number of Rings 8 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]- 249.275273 predictedDarkChem Lite v0.1.0 [M-H]- 223.44121 predictedDeepCCS 1.0 (2019) [M+H]+ 247.904073 predictedDarkChem Lite v0.1.0 [M+H]+ 225.3366 predictedDeepCCS 1.0 (2019) [M+Na]+ 249.506573 predictedDarkChem Lite v0.1.0 [M+Na]+ 231.383 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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
- Coppi G: [Dihydroergocristine. A review of pharmacology and toxicology]. Arzneimittelforschung. 1992 Nov;42(11A):1381-90. [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
- Coppi G: [Dihydroergocristine. A review of pharmacology and toxicology]. Arzneimittelforschung. 1992 Nov;42(11A):1381-90. [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
- Coppi G: [Dihydroergocristine. A review of pharmacology and toxicology]. Arzneimittelforschung. 1992 Nov;42(11A):1381-90. [Article]
- 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
- Coppi G: [Dihydroergocristine. A review of pharmacology and toxicology]. Arzneimittelforschung. 1992 Nov;42(11A):1381-90. [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]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Transporter activity
- Specific Function
- Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Drug created at June 23, 2017 20:40 / Updated at January 16, 2021 21:46