Identification
- Summary
Dihydro-alpha-ergocryptine 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
- Dihydro-alpha-ergocryptine
- DrugBank Accession Number
- DB11274
- Background
Alpha-dihydroergocryptine is usually referred to the mixture of the alpha and beta dihydroergocryptine. These two compounds are differentiated in the position of a methyl group. This structural difference is due to a proteinogenic amino acid replacement from leucine to isoleucine.16 Both compounds are hydrogenated ergot derivatives. Alpha-dihydroergocryptine approved drug product is as a part of an ergoloid mixture. To know more about this mixture, please visit Ergoloid mesylate
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Dihydro-alpha-ergocryptine (DB11274)
- Weight
- Average: 577.726
Monoisotopic: 577.326419505 - Chemical Formula
- C32H43N5O5
- Synonyms
- 9,10-dihydro-α-ergocryptine
- alpha-Dihydroergocriptine
- dihydro-α-ergocryptine
- α-dihydroergocryptine
Pharmacology
- Indication
Alpha-dihydroergocryptine has been studied for the early treatment of Parkinson disease2 as well as for its use in migraine prophylaxis,3 treatment of low blood pressure and peripheral vascular disorder. To know more about the ergoloid mesylate mixture and its uses 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 to treat Idiopathic parkinson's disease Regimen in combination with: Levodopa (DB01235) •••••••••••• Treatment of Idiopathic parkinson's disease •••••••••••• 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
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The effect of alpha-dihydroergocryptine in dopamine receptors was tested in PD patients and seem to generate a significant clinical improvement in the tested patients as well as to reduce motor complications and side effects.2 In long-term clinical trials with Parkinson disease patients, the administration of alpha-dihydroergocryptine and levodopa, the symptoms were reposted to improve or completely vanish in 80% of the tested individuals.8 All the registered effects of alpha-dihydroergocryptine suggest a potential neuroprotective effect of this drug and some reports have indicated that this activity may be related to the activation of NF-kB.10 The effect of alpha-dihydroergocryptine in the dopamine D2 receptor also reduces prolactin plasma levels and induce hypotension.9 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Mechanism of action
Alpha-dihydroergocryptine is an established high-affinity ligand to alpha 1 and alpha 2 adrenoreceptors in a number of tissues as well as a dopamine ligand in the brain.1 It is reported to be a potent agonist of the dopamine D2 receptor and a partial agonist of the dopamine receptors D1 and D3.4 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate and to know more about the isomer please visit Epicriptine.
Target Actions Organism ADopamine D2 receptor agonistHumans AD(1) dopamine receptor partial agonistHumans ADopamine D3 receptor partial agonistHumans - Absorption
Alpha-dihydroergocryptine is rapidly absorbed but it presents a very low bioavailability as it is part of a first-pass hepatic metabolism and thus less of 5% of the administered dose reaches blood circulation. The peak plasma concentration is attained after 30-120 minutes. The absorption of alpha-dihydroergocryptine is not affected by the co-administration with food.6 When administered in repeated oral doses the Cmax after 1 hour was registered to be 2157 pg/ml.7 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Volume of distribution
In preclinical studies, the volume of distribution after intravenous or oral administration was registered to be 11.054 L and 218.630 L respectively.14 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Protein binding
Alpha-dihydroergocryptine is highly bound to proteins and it has been reported to present a high affinity for intact human platelets.1 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Metabolism
Alpha-dihydroergocryptine presents a linear metabolism with the formation of active metabolites and the metabolism kinetics of this compound has no interference with L-dopa.9 It is highly metabolized with a rate of 2.4 ng/min/mg protein in the microsomal system and a formation of eight different metabolites.11 the metabolism of alpha-dihydroergocryptine seems to be highly marked by the action of CYP 3A4.12 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Route of elimination
Alpha-dihydroergocryptine is eliminated mainly by feces9 and to present a very low urinary excretion.13 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Half-life
Alpha-dihydroergocryptine has been studied in Parkinson disease models and it has shown a half-life of 12-16 hours.5 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Clearance
In preclinical studies, the clearance rate after intravenous or oral administration was registered to be 1.129 L/h and 25.98 L/h respectively.14 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate.
- Adverse Effects
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Alpha-dihydroergocryptine does not have effect in fertility and it does not present mutagenic potential.15 To know more about 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 Dihydro-alpha-ergocryptine can be increased when it is combined with Abametapir. Amiodarone The metabolism of Dihydro-alpha-ergocryptine can be decreased when combined with Amiodarone. Amprenavir The metabolism of Dihydro-alpha-ergocryptine can be decreased when combined with Amprenavir. Apalutamide The serum concentration of Dihydro-alpha-ergocryptine can be decreased when it is combined with Apalutamide. Aprepitant The metabolism of Dihydro-alpha-ergocryptine can be decreased when combined with Aprepitant. - 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 Dihydro-alpha-ergocryptine mesylate Z4I7BU58DN 14271-05-7 TZGKQIBPZOZAKF-PJLVGBPESA-N - Active Moieties
Name Kind UNII CAS InChI Key Dihydroergocryptine unknown 67V3FSL2GL Not Available Not applicable - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ergoloid Mesylates Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine mesylate (0.333 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 Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine mesylate (0.333 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 Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine mesylate (0.333 mg/1) + Dihydroergocristine mesylate (0.333 mg/1) + Epicriptine mesilate (0.111 mg/1) Tablet Oral Frontida BioPharm, Inc. 2017-06-01 Not applicable US Ergoloid Mesylates Dihydro-alpha-ergocryptine mesylate (0.333 mg/1) + Dihydroergocornine 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 Dihydro-alpha-ergocryptine mesylate (0.222 mg/1) + Dihydroergocornine mesylate (0.333 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
Categories
- Drug Categories
- 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 / Benzenoids 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 40 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- ergot alkaloid (CHEBI:59919)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 202229IR8Y
- CAS number
- 25447-66-9
- InChI Key
- PBUNVLRHZGSROC-VTIMJTGVSA-N
- InChI
- InChI=1S/C32H43N5O5/c1-17(2)12-25-29(39)36-11-7-10-26(36)32(41)37(25)30(40)31(42-32,18(3)4)34-28(38)20-13-22-21-8-6-9-23-27(21)19(15-33-23)14-24(22)35(5)16-20/h6,8-9,15,17-18,20,22,24-26,33,41H,7,10-14,16H2,1-5H3,(H,34,38)/t20-,22-,24-,25+,26+,31-,32+/m1/s1
- IUPAC Name
- (2R,4R,7R)-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-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](CC(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
- Elliott JM, Grahame-Smith DG: The binding characteristics of [3H]-dihydroergocryptine on intact human platelets. Br J Pharmacol. 1982 May;76(1):121-30. [Article]
- Battistin L, Bardin PG, Ferro-Milone F, Ravenna C, Toso V, Reboldi G: Alpha-dihydroergocryptine in Parkinson's disease: a multicentre randomized double blind parallel group study. Acta Neurol Scand. 1999 Jan;99(1):36-42. [Article]
- Micieli G, Cavallini A, Marcheselli S, Mailland F, Ambrosoli L, Nappi G: Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis. Int J Clin Pharmacol Ther. 2001 Apr;39(4):144-51. [Article]
- Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm (Vienna). 2003 Oct;110(10):1119-27. doi: 10.1007/s00702-003-0027-5. [Article]
- Antonini A, Tolosa E, Mizuno Y, Yamamoto M, Poewe WH: A reassessment of risks and benefits of dopamine agonists in Parkinson's disease. Lancet Neurol. 2009 Oct;8(10):929-37. doi: 10.1016/S1474-4422(09)70225-X. Epub 2009 Aug 24. [Article]
- Albanese A, Colosimo C: Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists. Acta Neurol Scand. 2003 May;107(5):349-55. [Article]
- de Mey C, Stamenova P, Daskalov M, Orozova M, Staikov I, Vlahov V, Wangemann M: Bioequivalence of a novel high-dose oral formulation of alpha-dihydroergocryptine. Arzneimittelforschung. 2006;56(3):205-11. doi: 10.1055/s-0031-1296712. [Article]
- Mailland E, Magnani P, Ottillinger B: Alpha-dihydroergocryptine in the long-term therapy of Parkinson's disease. Arzneimittelforschung. 2004;54(10):647-54. doi: 10.1055/s-0031-1297016. [Article]
- Authors unspecified: DA agonists -- ergot derivatives: dihydroergocryptine (DHEC): management of Parkinson's disease. Mov Disord. 2002;17 Suppl 4:S72-3. doi: 10.1002/mds.5564. [Article]
- Zheng SQ, Li T, Xuan YX, Lin SZ, Chen LJ, Yan GM: [Neuroprotective effect of alpha-dihydroergocryptine depends on activation of nuclear factor kappa B]. Yao Xue Xue Bao. 2000 Dec;35(12):898-901. [Article]
- Mas-Chamberlin C, Bromet N, Olgiati V, Girardello R, Lowenthal DT: Metabolism study of dihydro-alpha-ergocryptine,9,10-[9,10-3H(N)] in rat and human hepatocyte cultures and rat, monkey, and human microsomes. Am J Ther. 1997 Sep-Oct;4(9-10):291-9. [Article]
- de Mey C, Althaus M, Ezan E, Retzow A: Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans. Clin Pharmacol Ther. 2001 Aug;70(2):142-8. doi: 10.1067/mcp.2001.117286. [Article]
- Grognet JM, Istin M, Zanotti A, Mailland F, Coppi G: Pharmacokinetics of alpha-dihydroergokryptine in monkeys after oral administration. Drugs Exp Clin Res. 1991;17(6):309-12. [Article]
- Coppi G, Silingardi S: Pharmacokinetics of alpha-dihydroergocriptine in rats after single intravenous and single and repeated oral administrations. Biopharm Drug Dispos. 1995 May;16(4):333-42. [Article]
- Adams K, Allen JA, Brooker PC, Jones E, Proudlock RJ, Mailland F, Coppi G: Evaluation of the mutagenicity of a-dihydroergocryptine in vitro and in vivo. Arzneimittelforschung. 1993 Dec;43(12):1253-7. [Article]
- Steinhilber, D., Schubert M. and Roth H. (2005). Medizinische Chemie. Deutscher Apotheker Verlag. [ISBN:3-7692-3483-9]
- DIMDI Drug Product Information: Almirid-Cripar (dihydro-alpha-ergocryptine) oral tablets [Link]
- External Links
- ChemSpider
- 102887
- BindingDB
- 81453
- 91170
- ChEBI
- 59919
- ChEMBL
- CHEMBL1743263
- ZINC
- ZINC000003929793
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 20 MG Tablet 40 MG Tablet Oral Tablet, orally disintegrating Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 117 ºC LabNetwork boiling point (°C) Decomposes LabNetwork logP 5.90 Yasuda, et al. The Journal of Pharmacology and Experimental Therapeutics. (2002) - Predicted Properties
Property Value Source Water Solubility 0.264 mg/mL ALOGPS logP 3.28 ALOGPS logP 3.43 Chemaxon logS -3.3 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 157.33 m3·mol-1 Chemaxon Polarizability 64.05 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]- 240.6903502 predictedDarkChem Lite v0.1.0 [M-H]- 230.12173 predictedDeepCCS 1.0 (2019) [M+H]+ 239.3892502 predictedDarkChem Lite v0.1.0 [M+H]+ 232.01715 predictedDeepCCS 1.0 (2019) [M+Na]+ 239.4218502 predictedDarkChem Lite v0.1.0 [M+Na]+ 238.02214 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Potassium channel regulator activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
References
- Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm (Vienna). 2003 Oct;110(10):1119-27. doi: 10.1007/s00702-003-0027-5. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial 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
- Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm (Vienna). 2003 Oct;110(10):1119-27. doi: 10.1007/s00702-003-0027-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial agonist
- General Function
- G-protein coupled amine receptor activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
- Gene Name
- DRD3
- Uniprot ID
- P35462
- Uniprot Name
- D(3) dopamine receptor
- Molecular Weight
- 44224.335 Da
References
- Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm (Vienna). 2003 Oct;110(10):1119-27. doi: 10.1007/s00702-003-0027-5. [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
- de Mey C, Althaus M, Ezan E, Retzow A: Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans. Clin Pharmacol Ther. 2001 Aug;70(2):142-8. doi: 10.1067/mcp.2001.117286. [Article]
Drug created at December 03, 2015 16:52 / Updated at November 13, 2020 04:15