Dihydro-alpha-ergocryptine

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
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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatIdiopathic parkinson's diseaseRegimen in combination with: Levodopa (DB01235)••••••••••••
Treatment ofIdiopathic parkinson's disease••••••••••••
Used in combination for symptomatic treatment ofNo primary neurologial disease, idiopathic decreased mental activityCombination Product in combination with: Dihydroergocristine (DB13345), Dihydro-alpha-ergocryptine (DB11274)••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

TargetActionsOrganism
ADopamine D2 receptor
agonist
Humans
AD(1) dopamine receptor
partial agonist
Humans
ADopamine D3 receptor
partial agonist
Humans
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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Toxicity

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
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbametapirThe serum concentration of Dihydro-alpha-ergocryptine can be increased when it is combined with Abametapir.
AmiodaroneThe metabolism of Dihydro-alpha-ergocryptine can be decreased when combined with Amiodarone.
AmprenavirThe metabolism of Dihydro-alpha-ergocryptine can be decreased when combined with Amprenavir.
ApalutamideThe serum concentration of Dihydro-alpha-ergocryptine can be decreased when it is combined with Apalutamide.
AprepitantThe metabolism of Dihydro-alpha-ergocryptine can be decreased when combined with Aprepitant.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Dihydro-alpha-ergocryptine mesylateZ4I7BU58DN14271-05-7TZGKQIBPZOZAKF-PJLVGBPESA-N
Active Moieties
NameKindUNIICASInChI Key
Dihydroergocryptineunknown67V3FSL2GLNot AvailableNot applicable
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Ergoloid MesylatesDihydro-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)TabletOralCarilion Materials Management1991-10-31Not applicableUS flag
Ergoloid MesylatesDihydro-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)TabletOralPhysicians Total Care, Inc.1991-10-312012-10-08US flag
Ergoloid MesylatesDihydro-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)TabletOralFrontida BioPharm, Inc.2017-06-01Not applicableUS flag
Ergoloid MesylatesDihydro-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)TabletOralAv Kare, Inc.2014-08-222015-09-15US flag
Ergoloid MesylatesDihydro-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)TabletOralSun Pharmaceutical Industries Limited1991-10-31Not applicableUS flag

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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. Steinhilber, D., Schubert M. and Roth H. (2005). Medizinische Chemie. Deutscher Apotheker Verlag. [ISBN:3-7692-3483-9]
  17. DIMDI Drug Product Information: Almirid-Cripar (dihydro-alpha-ergocryptine) oral tablets [Link]
ChemSpider
102887
BindingDB
81453
RxNav
91170
ChEBI
59919
ChEMBL
CHEMBL1743263
ZINC
ZINC000003929793

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet20 MG
Tablet40 MG
TabletOral
Tablet, orally disintegratingOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)117 ºCLabNetwork
boiling point (°C)DecomposesLabNetwork
logP5.90Yasuda, et al. The Journal of Pharmacology and Experimental Therapeutics. (2002)
Predicted Properties
PropertyValueSource
Water Solubility0.264 mg/mLALOGPS
logP3.28ALOGPS
logP3.43Chemaxon
logS-3.3ALOGPS
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 Count5Chemaxon
Refractivity157.33 m3·mol-1Chemaxon
Polarizability64.05 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/MSsplash10-004i-0000090000-6bf55b1c83e16ac7d2fa
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0000090000-e7b4be9f3bf08fc2ffa0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004j-1090070000-64477b45b00dbd4e2ac1
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0063090000-94869e0770f2d90b638e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fi0-1094010000-b29406ddb39239519495
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-056r-1091020000-7350b157a23e73c27808
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-240.6903502
predicted
DarkChem Lite v0.1.0
[M-H]-230.12173
predicted
DeepCCS 1.0 (2019)
[M+H]+239.3892502
predicted
DarkChem Lite v0.1.0
[M+H]+232.01715
predicted
DeepCCS 1.0 (2019)
[M+Na]+239.4218502
predicted
DarkChem Lite v0.1.0
[M+Na]+238.02214
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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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
  1. 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
  1. 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
  1. 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
  1. 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