Basic Info

Common NameCotinine(F05158)
2D Structure
Description

Quantitatively, the most important metabolite of nicotine in most mammalian species is cotinine. In humans, about 70 to 80% of nicotine is converted to cotinine. This transformation involves two steps. The first is mediated by a cytochrome P450 system (mainly CYP2A6 and CYP2B6) to produce nicotine iminium ion. The second step is catalyzed by aldehyde oxidase (AOX). A number of cotinine metabolites have also been structurally characterized. Indeed, it appears that most of the reported urinary metabolites of nicotine are derived from cotinine.

FRCD IDF05158
CAS Number486-56-6
PubChem CID408
FormulaC10H12N2O
IUPAC Name

1-methyl-5-pyridin-3-ylpyrrolidin-2-one

InChI Key

UIKROCXWUNQSPJ-UHFFFAOYSA-N

InChI

InChI=1S/C10H12N2O/c1-12-9(4-5-10(12)13)8-3-2-6-11-7-8/h2-3,6-7,9H,4-5H2,1H3

Canonical SMILES

CN1C(CCC1=O)C2=CN=CC=C2

Isomeric SMILES

CN1C(CCC1=O)C2=CN=CC=C2

WikipediaCotinine
Synonyms
        
            1-Methyl-5-(3-pyridinyl)-2-pyrrolidinone
        
            rac Cotinine
        
            15569-85-4
        
            2-Pyrrolidinone, 1-methyl-5-(3-pyridinyl)-
        
            rac-Cotinine
        
            S-(-)-Cotinine
        
            (S)-Cotinine
        
            CHEMBL664
        
            2-Pyrrolidinone, 1-methyl-5-(3-pyridinyl)-, (S)-
        
            1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
        
Classifies
                

                  
                    Animal Toxin
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganoheterocyclic compounds
ClassPyridines and derivatives
SubclassPyrrolidinylpyridines
Intermediate Tree NodesNot available
Direct ParentPyrrolidinylpyridines
Alternative Parents
Molecular FrameworkAromatic heteromonocyclic compounds
SubstituentsPyrrolidinylpyridine - Alkaloid or derivatives - Pyrrolidone - 2-pyrrolidone - N-alkylpyrrolidine - Pyrrolidine - Tertiary carboxylic acid amide - Heteroaromatic compound - Lactam - Carboxamide group - Carboxylic acid derivative - Azacycle - Organic oxide - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Aromatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as pyrrolidinylpyridines. These are compounds containing a pyrrolidinylpyridine ring system, which consists of a pyrrolidine ring linked to a pyridine ring.

Properties

Property NameProperty Value
Molecular Weight176.219
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count1
Complexity205
Monoisotopic Mass176.095
Exact Mass176.095
XLogP-0.3
Formal Charge0
Heavy Atom Count13
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9845
Human Intestinal AbsorptionHIA+0.9913
Caco-2 PermeabilityCaco2+0.7612
P-glycoprotein SubstrateNon-substrate0.7711
P-glycoprotein InhibitorNon-inhibitor0.7427
Non-inhibitor0.9538
Renal Organic Cation TransporterNon-inhibitor0.5483
Distribution
Subcellular localizationMitochondria0.7328
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7327
CYP450 2D6 SubstrateNon-substrate0.9116
CYP450 3A4 SubstrateSubstrate0.5931
CYP450 1A2 InhibitorNon-inhibitor0.9046
CYP450 2C9 InhibitorNon-inhibitor0.9071
CYP450 2D6 InhibitorNon-inhibitor0.9230
CYP450 2C19 InhibitorNon-inhibitor0.9099
CYP450 3A4 InhibitorNon-inhibitor0.9169
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.8746
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9810
Non-inhibitor0.9133
AMES ToxicityNon AMES toxic0.9672
CarcinogensNon-carcinogens0.9572
Fish ToxicityLow FHMT0.8584
Tetrahymena Pyriformis ToxicityLow TPT0.8274
Honey Bee ToxicityLow HBT0.8669
BiodegradationNot ready biodegradable0.9224
Acute Oral ToxicityIII0.5619
Carcinogenicity (Three-class)Non-required0.6720

Model Value Unit
Absorption
Aqueous solubility-0.0015LogS
Caco-2 Permeability1.2947LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.4452LD50, mol/kg
Fish Toxicity1.8829pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.1004pIGC50, ug/L

References

TitleJournalDatePubmed ID
Detoxification and elimination of nicotine by nectar-feeding birds.J Comp Physiol B2017 May28150179
A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection.Toxins (Basel)2017 Mar 1028287432
Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank.J Hum Lact2016 Aug27197576
Tobacco smoking-response genes in blood and buccal cells.Toxicol Lett2015 Jan 2225447457
Biomarkers of exposure among U.S. cigar smokers: an analysis of 1999-2012 National Health and Nutrition Examination Survey (NHANES) data.Cancer Epidemiol Biomarkers Prev2014 Dec25380733
Development of an experimental model for assessing the effects of cigarette smoke and virus infections on inflammatory responses to bacterial antigens.Innate Immun2014 Aug24137042
Runoff of pharmaceuticals and personal care products following application of dewatered municipal biosolids to an agricultural field.Sci Total Environ2009 Aug 119464726
The influence of gender, race, and menthol content on tobacco exposure measures.Nicotine Tob Res2005 Aug16085529
Smoking reduction promotes smoking cessation: results from a double blind, randomized, placebo-controlled trial of nicotine gum with 2-year follow-up.Addiction2003 Oct14519176
Optimization study for the reversed-phase ion-pair liquid chromatographic determination of nicotine in commercial tobacco products.J Chromatogr A1999 Aug 1310481983
Nicotine gum dose and weight gain after smoking cessation.J Consult Clin Psychol1996 Aug8803371
Nontobacco sources of cotinine in the urine of nonsmokers.Clin Pharmacol Ther1995 Apr7712678
Smokeless tobacco abstinence effects and nicotine gum dose.Psychopharmacology (Berl)19921738794

Targets

General Function:
Toxic substance binding
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
Gene Name:
CHRNA7
Uniprot ID:
P36544
Molecular Weight:
56448.925 Da
References
  1. Briggs CA, McKenna DG, Monteggia LM, Touma E, Roch JM, Arneric SP, Gopalakrishnan M, Sullivan JP: Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant. Eur J Pharmacol. 1999 Feb 5;366(2-3):301-8. [10082212 ]