Identification

Name
Nicergoline
Accession Number
DB00699
Description

An ergot derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. It has been suggested to ameliorate cognitive deficits in cerebrovascular disease.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 484.386
Monoisotopic: 483.11575436
Chemical Formula
C24H26BrN3O3
Synonyms
  • (8β)-10-methoxy-1,6-dimethylergoline-8-methanol 5-bromo-3-pyridinecarboxylate (ester)
  • 10-methoxy-1,6-dimethylergoline-8β-methanol 5-bromonicotinate
  • Nicergolin
  • Nicergolina
  • Nicergoline
  • Nicergolinum
External IDs
  • FI-6714

Pharmacology

Indication

For the treatment of senile dementia, migraines of vascular origin, transient ischemia, platelet hyper-aggregability, and macular degeneration.

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Nicergoline is a potent vasodilator (improves brain blood flow). On the cerebral level it prompts a lowering of vascular resistance, an increase in arterial flow and stimulates the use of oxygen and glucose. Nicergoline also improves blood circulation in the lungs and limbs and has been shown to inhibit blood platelet aggregation.

Mechanism of action

Nicergoline acts by inhibiting the postsynaptic alpha(1)-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation. Therefore the mechanism of Nicergoline is to increase vascular circulation in the brain, thereby enhancing the transmission of nerve signals across the nerve fibres, which secrete acetylcholine as a neural transmitter.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hover over products below to view reaction partners

Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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
AbataceptThe metabolism of Nicergoline can be increased when combined with Abatacept.
AbirateroneThe metabolism of Nicergoline can be decreased when combined with Abiraterone.
AcebutololAcebutolol may increase the vasoconstricting activities of Nicergoline.
AceclofenacThe risk or severity of hypertension can be increased when Nicergoline is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Nicergoline is combined with Acemetacin.
AcetaminophenThe metabolism of Nicergoline can be decreased when combined with Acetaminophen.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Nicergoline is combined with Acetylsalicylic acid.
AdalimumabThe metabolism of Nicergoline can be increased when combined with Adalimumab.
AlclofenacThe risk or severity of hypertension can be increased when Nicergoline is combined with Alclofenac.
AlfentanilThe risk or severity of hypertension can be increased when Nicergoline is combined with Alfentanil.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
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Food Interactions
Not Available

Products

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International/Other Brands
Sermion

Categories

ATC Codes
C04AE02 — Nicergoline
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Indoloquinolines
Direct Parent
Indoloquinolines
Alternative Parents
Ergoline and derivatives / Benzoquinolines / Pyrroloquinolines / 3-alkylindoles / N-alkylindoles / Pyridinecarboxylic acids / Isoindoles and derivatives / Aralkylamines / Piperidines / N-methylpyrroles
show 13 more
Substituents
3-alkylindole / Alkaloid or derivatives / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Aryl bromide / Aryl halide / Azacycle / Benzenoid
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
JCV8365FWN
CAS number
27848-84-6
InChI Key
YSEXMKHXIOCEJA-FVFQAYNVSA-N
InChI
InChI=1S/C24H26BrN3O3/c1-27-13-17-8-21-24(30-3,19-5-4-6-20(27)22(17)19)9-15(12-28(21)2)14-31-23(29)16-7-18(25)11-26-10-16/h4-7,10-11,13,15,21H,8-9,12,14H2,1-3H3/t15-,21-,24+/m1/s1
IUPAC Name
[(2S,4R,7R)-2-methoxy-6,11-dimethyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraen-4-yl]methyl 5-bromopyridine-3-carboxylate
SMILES
[H][[email protected]@]12CC3=CN(C)C4=CC=CC(=C34)[[email protected]]1(C[[email protected]@H](COC(=O)C1=CN=CC(Br)=C1)CN2C)OC

References

General References
  1. Winblad B, Fioravanti M, Dolezal T, Logina I, Milanov IG, Popescu DC, Solomon A: Therapeutic use of nicergoline. Clin Drug Investig. 2008;28(9):533-52. [PubMed:18666801]
Human Metabolome Database
HMDB0014837
KEGG Drug
D01290
PubChem Compound
34040
PubChem Substance
46508741
ChemSpider
31373
RxNav
7398
ChEBI
31902
ChEMBL
CHEMBL1372950
ZINC
ZINC000003873817
Therapeutic Targets Database
DAP000902
PharmGKB
PA164743014
Wikipedia
Nicergoline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentAnxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia1
1Active Not RecruitingOtherPharmacokinetics1
Not AvailableCompletedNot AvailableAlzheimer's Disease (AD) / Dementia / Dementia, Vascular1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, coatedOral30 mg
Tablet, film coatedOral10 MG
Tablet, film coatedOral30 MG
Tablet, coatedOral10 mg
Tablet, sugar coatedOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0127 mg/mLALOGPS
logP3.99ALOGPS
logP3.7ChemAxon
logS-4.6ALOGPS
pKa (Strongest Basic)8.12ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area56.59 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity123.3 m3·mol-1ChemAxon
Polarizability48.08 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9908
Blood Brain Barrier+0.9396
Caco-2 permeable+0.5782
P-glycoprotein substrateSubstrate0.7569
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.9233
Renal organic cation transporterInhibitor0.5733
CYP450 2C9 substrateNon-substrate0.8512
CYP450 2D6 substrateNon-substrate0.7141
CYP450 3A4 substrateSubstrate0.6869
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8126
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5988
Ames testNon AMES toxic0.7004
CarcinogenicityNon-carcinogens0.9091
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6401 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.914
hERG inhibition (predictor II)Inhibitor0.5933
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Alvarez-Guerra M, Bertholom N, Garay RP: Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha 1A-adrenoceptor subtype in the rat. Fundam Clin Pharmacol. 1999;13(1):50-8. [PubMed:10027088]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Bottiger Y, Dostert P, Benedetti MS, Bani M, Fiorentini F, Casati M, Poggesti I, Alm C, Alvan G, Bertilsson L: Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans. Br J Clin Pharmacol. 1996 Dec;42(6):707-11. [PubMed:8971425]
  2. Saletu B, Garg A, Shoeb A: Safety of nicergoline as an agent for management of cognitive function disorders. Biomed Res Int. 2014;2014:610103. doi: 10.1155/2014/610103. Epub 2014 Aug 28. [PubMed:25243157]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2020 20:51

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