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Identification
NameNicergoline
Accession NumberDB00699  (APRD00617)
TypeSmall Molecule
GroupsApproved
DescriptionAn 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 Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
SermionNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIJCV8365FWN
CAS number27848-84-6
WeightAverage: 484.386
Monoisotopic: 483.11575436
Chemical FormulaC24H26BrN3O3
InChI KeyYSEXMKHXIOCEJA-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
IndicationFor the treatment of senile dementia, migraines of vascular origin, transient ischemia, platelet hyper-aggregability, and macular degeneration.
Structured Indications Not Available
PharmacodynamicsNicergoline 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 actionNicergoline 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Alpha-1A adrenergic receptorProteinyes
antagonist
HumanP35348 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Nicergoline
10-alpha-methoxy-9,10-dihydrolysergolDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot 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.Approved
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 InteractionsNot Available
References
Synthesis ReferenceNot 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
ATC CodesC04AE02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassIndoloquinolines
Direct ParentIndoloquinolines
Alternative Parents
Substituents
  • Indoloquinoline
  • Ergoline skeleton
  • Benzoquinoline
  • Pyrroloquinoline
  • Alkaloid or derivatives
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Isoindole or derivatives
  • Indole or derivatives
  • Indole
  • Aralkylamine
  • Benzenoid
  • Substituted pyrrole
  • Pyridine
  • Piperidine
  • N-methylpyrrole
  • Aryl halide
  • Aryl bromide
  • Heteroaromatic compound
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23