Cotinine (T3D3956)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 04:47:10 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3956
Identification
Common NameCotinine
ClassSmall Molecule
DescriptionQuantitatively, 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.
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Food Toxin
  • Industrial/Workplace Toxin
  • Mammal Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(-)-Cotinine
(S)-(-)-Cotinine
(S)-Cotinine
Cotinina
Cotininum
S-(-)-Cotinine
Chemical FormulaC10H12N2O
Average Molecular Mass176.215 g/mol
Monoisotopic Mass176.095 g/mol
CAS Registry Number486-56-6
IUPAC Name1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
Traditional Name(-)-cotinine
SMILESCN1C(CCC1=O)C1=CN=CC=C1
InChI IdentifierInChI=1/C10H12N2O/c1-12-9(4-5-10(12)13)8-3-2-6-11-7-8/h2-3,6-7,9H,4-5H2,1H3
InChI KeyInChIKey=UIKROCXWUNQSPJ-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrrolidinylpyridines. Pyrrolidinylpyridines are compounds containing a pyrrolidinylpyridine ring system, which consists of a pyrrolidine ring linked to a pyridine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyrrolidinylpyridines
Direct ParentPyrrolidinylpyridines
Alternative Parents
Substituents
  • Pyrrolidinylpyridine
  • 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
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Brain
  • Cervical
  • Hair
  • Kidney
  • Liver
  • Placenta
  • Platelet
  • Testes
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point41°C
Boiling PointNot Available
SolubilityNot Available
LogP0.07
Predicted Properties
PropertyValueSource
Water Solubility117 g/LALOGPS
logP0.39ALOGPS
logP0.21ChemAxon
logS-0.18ALOGPS
pKa (Strongest Basic)4.79ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area33.2 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity49.28 m³·mol⁻¹ChemAxon
Polarizability18.57 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-9500000000-f031a7d223ea527c7a802017-09-12View Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-004i-0900000000-61e8e1349a9d428662602017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-9500000000-f031a7d223ea527c7a802018-05-18View Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-004i-0900000000-61e8e1349a9d428662602018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0gdl-6900000000-7eb4053aab6127e953912017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-2900000000-7f61a2f6f72860e4c6e12012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9100000000-3a5b30b90a390122b8682012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-b82772b6f28d39966cd12012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-60) , Positivesplash10-0002-9500000000-e8a00bc1cf980c18ed062012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - CI-B (HITACHI M-60) , Positivesplash10-004i-0900000000-61e8e1349a9d428662602012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-16fb662f236943b7061e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-bb6734f53ed607f8551f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-3900000000-b7fe72bb7584aa19a7362017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-2900000000-bb9334268373122b4f812017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-004i-0900000000-bb6734f53ed607f8551f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004i-3900000000-617e9ef99f5ff220e7f92021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004i-3900000000-1ad4398aa27830eabbbd2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-3210604d5a8368e435a02021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-785e2933ae8dc3d4b2972021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-4be8a9d2dee773690bd32021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-001j-9100000000-8081f3e6f95787810baa2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-a4a59884dbcf842f195a2015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1900000000-0cfe8e8d340c82c8fd112015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0k9y-9500000000-e18e0cea3d758c6ff7682015-04-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-6fcf3e50bea7e8c250082015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0900000000-dad0516bb0862355ae612015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05r4-9700000000-36486e0d1769fb592c7a2015-04-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-55ef895c84a338046aba2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1900000000-72acff4eea7467f916132021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9800000000-8b60e7a4fd9931166f142021-09-22View Spectrum
MSMass Spectrum (Electron Ionization)splash10-002b-9600000000-0cc3afdaebb529092e242014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureInhalation
Mechanism of ToxicityNot Available
MetabolismCotinine is a metabolite of nicotine. Cotinine has an in vivo half-life of approximately 20 hours, and is typically detectable for several days (up to one week) after the use of tobacco. The level of cotinine in the blood is proportionate to the amount of exposure to tobacco smoke, so it is a valuable indicator of tobacco smoke exposure, including secondary (passive) smoke. People who smoke menthol cigarettes may retain cotinine in the blood for a longer period because menthol can compete with enzymatic metabolism of cotinine. (Wikipedia)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesCotinine is an alkaloid found in tobacco and is also a metabolite of nicotine. (Wikipedia)
Minimum Risk LevelNot Available
Health EffectsSimilarly to nicotine, cotinine binds to, activates, and desensitizes neuronal nicotinic acetylcholine receptors, though at much lower potency in comparison. It has demonstrated nootropic and antipsychotic-like effects in animal models. Direct administration of high levels of cotinine resulted in no significant physiologic, subjective, or performance effects. (Wikipedia)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB01046
PubChem Compound ID408
ChEMBL IDCHEMBL664
ChemSpider ID395
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID127762
BioCyc IDCPD-2742
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCotinine
References
Synthesis ReferenceRolf, David; Goon, David J. W.; Michelson, Robert H. Preparation of cotinine by reacting nicotine with bromide and bromate. U.S. (1997), 5 pp.
MSDSLink
General References
  1. Bentley MC, Abrar M, Kelk M, Cook J, Phillips K: Validation of an assay for the determination of cotinine and 3-hydroxycotinine in human saliva using automated solid-phase extraction and liquid chromatography with tandem mass spectrometric detection. J Chromatogr B Biomed Sci Appl. 1999 Feb 19;723(1-2):185-94. [10080645 ]
  2. Urakawa N, Nagata T, Kudo K, Kimura K, Imamura T: Simultaneous determination of nicotine and cotinine in various human tissues using capillary gas chromatography/mass spectrometry. Int J Legal Med. 1994;106(5):232-6. [8068568 ]
  3. Poppe WA, Peeters R, Drijkoningen M, Ide PS, Daenens P, Lauweryns JM, Van Assche FA: Cervical cotinine and macrophage-Langerhans cell density in the normal human uterine cervix. Gynecol Obstet Invest. 1996;41(4):253-9. [8793496 ]
  4. Jacqz-Aigrain E, Zhang D, Maillard G, Luton D, Andre J, Oury JF: Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair. BJOG. 2002 Aug;109(8):909-11. [12197371 ]
  5. Gwent SH, Wilson JF, Tsanaclis LM, Wicks JF: Time course of appearance of cotinine in human beard hair after a single dose of nicotine. Ther Drug Monit. 1995 Apr;17(2):195-8. [7624910 ]
  6. Dobek D, Karmowski A, Sobiech KA, Terpilowski L, Mis-Michalek M: Average quantitative concentration of cotinine within the system pregnant woman-baby. Arch Immunol Ther Exp (Warsz). 1998;46(1):59-61. [9510948 ]
  7. Torano JS, van Kan HJ: Simultaneous determination of the tobacco smoke uptake parameters nicotine, cotinine and thiocyanate in urine, saliva and hair, using gas chromatography-mass spectrometry for characterisation of smoking status of recently exposed subjects. Analyst. 2003 Jul;128(7):838-43. [12894819 ]
  8. Knight JM, Eliopoulos C, Klein J, Greenwald M, Koren G: Passive smoking in children. Racial differences in systemic exposure to cotinine by hair and urine analysis. Chest. 1996 Feb;109(2):446-50. [8620720 ]
  9. Hatsukami DK, Jensen J, Brauer LH, Mooney M, Schulte S, Sofuoglu M, Pentel PR: Lack of effect of 5HT3 antagonist in mediating subjective and behavioral responses to cotinine. Pharmacol Biochem Behav. 2003 Apr;75(1):1-7. [12759107 ]
  10. Laskowska-Klita T, Chelchowska M, Leibschang J: [Concentrations of cotinine in serum and urine of smoking pregnant women and in placenta and umbilical cord blood]. Przegl Lek. 2005;62(10):1007-9. [16521941 ]
  11. Nicotine absorption by workers harvesting green tobacco. Lancet. 1975 Mar 1;1(7905):478-80. [46956 ]
  12. Tutka P, Wielosz M, Zatonski W: Exposure to environmental tobacco smoke and children health. Int J Occup Med Environ Health. 2002;15(4):325-35. [12608620 ]
  13. Paszkowski T: [Concentration gradient of cotinine between blood serum and preovulatory follicular fluid]. Ginekol Pol. 1998 Dec;69(12):1131-6. [10224789 ]
  14. Poppe WA, Peeters R, Daenens P, Ide PS, Van Assche FA: Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical fluid. Gynecol Obstet Invest. 1995;39(2):110-4. [7737579 ]
  15. Istvan JA, Lee WW, Buist AS, Connett JE: Relation of salivary cotinine to blood pressure in middle-aged cigarette smokers. Am Heart J. 1999 May;137(5):928-31. [10220643 ]
  16. Nafstad P, Botten G, Hagen JA, Zahlsen K, Nilsen OG, Silsand T, Kongerud J: Comparison of three methods for estimating environmental tobacco smoke exposure among children aged between 12 and 36 months. Int J Epidemiol. 1995 Feb;24(1):88-94. [7797361 ]
  17. Eliopoulos C, Klein J, Chitayat D, Greenwald M, Koren G: Nicotine and cotinine in maternal and neonatal hair as markers of gestational smoking. Clin Invest Med. 1996 Aug;19(4):231-42. [8853571 ]
  18. Eliopoulos C, Klein J, Koren G: Validation of self-reported smoking by analysis of hair for nicotine and cotinine. Ther Drug Monit. 1996 Oct;18(5):532-6. [8885115 ]
  19. Wilson SE, Kahn RS, Khoury J, Lanphear BP: Racial differences in exposure to environmental tobacco smoke among children. Environ Health Perspect. 2005 Mar;113(3):362-7. [15743729 ]
  20. Kintz P: Gas chromatographic analysis of nicotine and cotinine in hair. J Chromatogr. 1992 Sep 16;580(1-2):347-53. [1400830 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Neuronal acetylcholine receptor subunit alpha-7
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 ]