Nicergoline

Identification

Name
Nicergoline
Accession Number
DB00699  (APRD00617)
Type
Small Molecule
Groups
Approved
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. [PubChem]

Structure
Thumb
Synonyms
  • Nicergolin
  • Nicergolina
  • Nicergoline
  • Nicergolinum
  • Sermion
External IDs
FI-6714
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Sermion
Brand mixtures
Not Available
Categories
UNII
JCV8365FWN
CAS number
27848-84-6
Weight
Average: 484.386
Monoisotopic: 483.11575436
Chemical Formula
C24H26BrN3O3
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[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),9,12,14-tetraen-4-yl]methyl 5-bromopyridine-3-carboxylate
SMILES
[H][C@@]12CC3=CN(C)C4=CC=CC(=C34)[C@]1(C[C@@H](COC(=O)C1=CC(Br)=CN=C1)CN2C)OC

Pharmacology

Indication

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

Structured Indications
Not Available
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
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Nicergoline can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe metabolism of Nicergoline can be decreased when combined with Amiodarone.Approved, Investigational
ArtemetherThe metabolism of Nicergoline can be decreased when combined with Artemether.Approved
AtomoxetineThe metabolism of Nicergoline can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Nicergoline can be decreased when combined with Betaxolol.Approved
BupropionThe metabolism of Nicergoline can be decreased when combined with Bupropion.Approved
CelecoxibThe metabolism of Nicergoline can be decreased when combined with Celecoxib.Approved, Investigational
ChloroquineThe metabolism of Nicergoline can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Nicergoline can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Nicergoline can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Nicergoline can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Nicergoline can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Nicergoline can be decreased when combined with Citalopram.Approved
ClemastineThe metabolism of Nicergoline can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Nicergoline can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Nicergoline can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Nicergoline can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Nicergoline can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Nicergoline can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Nicergoline can be decreased when combined with Cocaine.Approved, Illicit
DarifenacinThe metabolism of Nicergoline can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Nicergoline can be increased when it is combined with Darunavir.Approved
DelavirdineThe metabolism of Nicergoline can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Nicergoline can be decreased when combined with Desipramine.Approved
DiphenhydramineThe metabolism of Nicergoline can be decreased when combined with Diphenhydramine.Approved
DronedaroneThe metabolism of Nicergoline can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Nicergoline can be decreased when combined with Duloxetine.Approved
EliglustatThe metabolism of Nicergoline can be decreased when combined with Eliglustat.Approved
FluoxetineThe metabolism of Nicergoline can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Nicergoline can be decreased when combined with Fluvoxamine.Approved, Investigational
HaloperidolThe metabolism of Nicergoline can be decreased when combined with Haloperidol.Approved
ImipramineThe metabolism of Nicergoline can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Nicergoline can be decreased when combined with Indinavir.Approved
IsoniazidThe metabolism of Nicergoline can be decreased when combined with Isoniazid.Approved
KetoconazoleThe metabolism of Nicergoline can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Nicergoline can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Nicergoline can be decreased when combined with Lorcaserin.Approved
LumefantrineThe metabolism of Nicergoline can be decreased when combined with Lumefantrine.Approved
MethadoneThe metabolism of Nicergoline can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Nicergoline can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Nicergoline can be decreased when combined with Metoprolol.Approved, Investigational
MirabegronThe metabolism of Nicergoline can be decreased when combined with Mirabegron.Approved
NevirapineThe metabolism of Nicergoline can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Nicergoline can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Nicergoline can be decreased when combined with Nilotinib.Approved, Investigational
PanobinostatThe serum concentration of Nicergoline can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Nicergoline can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Nicergoline can be decreased when it is combined with Peginterferon alfa-2b.Approved
PromazineThe metabolism of Nicergoline can be decreased when combined with Promazine.Approved, Vet Approved
QuinidineThe metabolism of Nicergoline can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Nicergoline can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Nicergoline can be decreased when combined with Ranolazine.Approved, Investigational
RitonavirThe metabolism of Nicergoline can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Nicergoline can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Nicergoline can be decreased when combined with Ropinirole.Approved, Investigational
SertralineThe metabolism of Nicergoline can be decreased when combined with Sertraline.Approved
StiripentolThe metabolism of Nicergoline can be decreased when combined with Stiripentol.Approved
TerbinafineThe metabolism of Nicergoline can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
ThioridazineThe metabolism of Nicergoline can be decreased when combined with Thioridazine.Withdrawn
TiclopidineThe metabolism of Nicergoline can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Nicergoline can be decreased when combined with Tipranavir.Approved, Investigational
TranylcypromineThe metabolism of Nicergoline can be decreased when combined with Tranylcypromine.Approved
VenlafaxineThe metabolism of Nicergoline can be decreased when combined with Venlafaxine.Approved
ZiprasidoneThe metabolism of Nicergoline can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

Synthesis Reference
Not Available
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 ]
External Links
Human Metabolome Database
HMDB14837
KEGG Drug
D01290
PubChem Compound
34040
PubChem Substance
46508741
ChemSpider
31373
ChEBI
31902
ChEMBL
CHEMBL1372950
Therapeutic Targets Database
DAP000902
PharmGKB
PA164743014
Wikipedia
Nicergoline
ATC Codes
C04AE02 — Nicergoline
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentAnxiety Disorder / Dementias / Depressive State / Psychosomatic Disorders / Schizophrenic Disorders1
4CompletedNot AvailableAlzheimer's Disease (AD) / Dementia, Vascular / Dementias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
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)8.14ChemAxon
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 LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of chemical entities known as indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Organoheterocyclic compounds
Sub Class
Quinolines and derivatives
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
Ergoline skeleton / Indoloquinoline / Benzoquinoline / Pyrroloquinoline / N-alkylindole / 3-alkylindole / Indole / Indole or derivatives / Isoindole or derivatives / Pyridine carboxylic acid
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:31