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Identification
NameNicergoline
Accession NumberDB00699  (APRD00617)
Typesmall molecule
Groupsapproved
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
SynonymLanguageCode
NicergolinGermanNot Available
NicergolinaNot AvailableDCIT
NicergolineNot AvailableINN, BAN, USAN, JAN
NicergolinumLatinINN
SaltsNot Available
Brand names
NameCompany
SermionNot Available
Brand mixturesNot Available
Categories
CAS number27848-84-6
WeightAverage: 484.386
Monoisotopic: 483.11575436
Chemical FormulaC24H26BrN3O3
InChI KeyInChIKey=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][C@@]12CC3=CN(C)C4=CC=CC(=C34)[C@]1(C[C@@H](COC(=O)C1=CC(Br)=CN=C1)CN2C)OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassIndoloquinolines
Direct parentIndoloquinolines
Alternative parentsBenzoquinolines; Pyrroloquinolines; Pyridinecarboxylic Acids; Isoindoles and Derivatives; Indoles; Aryl Bromides; N-methylpyrroles; Piperidines; Benzene and Substituted Derivatives; Carboxylic Acid Esters; Tertiary Amines; Dialkyl Ethers; Enolates; Polyamines; Organobromides; Ergoline Derivatives
Substituentsbenzoquinoline; pyrroloquinoline; indole; indole or derivative; isoindole or derivative; pyridine carboxylic acid or derivative; pyridine carboxylic acid; n-methylpyrrole; n-substituted pyrrole; benzene; aryl halide; pyridine; piperidine; substituted pyrrole; aryl bromide; pyrrole; tertiary amine; carboxylic acid ester; polyamine; enolate; carboxylic acid derivative; dialkyl ether; ether; amine; organonitrogen compound; organobromide; organohalogen
Classification descriptionThis compound belongs to the indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
Pharmacology
IndicationFor the treatment of senile dementia, migraines of vascular origin, transient ischemia, platelet hyper-aggregability, and macular degeneration.
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.
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
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9908
Blood Brain Barrier + 0.9396
Caco-2 permeable + 0.5782
P-glycoprotein substrate Substrate 0.7569
P-glycoprotein inhibitor I Inhibitor 0.8563
P-glycoprotein inhibitor II Inhibitor 0.9233
Renal organic cation transporter Inhibitor 0.5733
CYP450 2C9 substrate Non-substrate 0.8512
CYP450 2D6 substrate Non-substrate 0.7141
CYP450 3A4 substrate Substrate 0.6869
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9072
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.8126
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5988
Ames test Non AMES toxic 0.7004
Carcinogenicity Non-carcinogens 0.9091
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.6401 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.914
hERG inhibition (predictor II) Inhibitor 0.5933
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP3.3Not Available
Predicted Properties
PropertyValueSource
water solubility1.27e-02 g/lALOGPS
logP3.99ALOGPS
logP3.7ChemAxon
logS-4.6ALOGPS
pKa (strongest basic)8.14ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count0ChemAxon
polar surface area56.59ChemAxon
rotatable bond count5ChemAxon
refractivity123.3ChemAxon
polarizability48.08ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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
ResourceLink
KEGG DrugD01290
PubChem Compound34040
PubChem Substance46508741
ChemSpider31373
Therapeutic Targets DatabaseDAP000902
PharmGKBPA164743014
WikipediaNicergoline
ATC CodesC04AE02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11