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Record Information
StatusExpected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-02-26 21:23:25 UTC
Secondary Accession Numbers
  • HMDB01497
Metabolite Identification
Common NameNicotine-1'-N-oxide
DescriptionNicotine-1'-N-oxide, also known as 1'-oxide nicotine, 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. It appears that NNO is not further metabolized to any significant extent, except by reduction back to nicotine, which may lead to recycling of nicotine in the body. The conversion of nicotine to NNO involves a flavin-containing monooxygenase 3 (FMO3). Nicotine-1'-N-oxide is a strong basic compound (based on its pKa). nicotine-1'-N-oxide can be biosynthesized from nicotine through its interaction with the enzyme dimethylaniline monooxygenase [N-oxide-forming] 3. In humans, nicotine-1'-N-oxide is involved in nicotine metabolism pathway. Outside of the human body, Nicotine-1'-N-oxide has been detected, but not quantified in, several different foods, such as red rices, coconuts, chinese broccoli, corn salad, and rowanberries. This could make nicotine-1'-N-oxide a potential biomarker for the consumption of these foods. Nicotine N'-oxide (NNO) is a primary metabolite of nicotine, although only about 4-7% of nicotine absorbed by smokers is metabolized via this route.
Nicotine 1-N-oxideChEBI
1-Methyl-2-(3-pyridyl)-2,3,4,5-tetrahydropyrrol-1-olic acidGenerator
(2S)-N-Oxide 3-(1-methyl-2-pyrrolidinyl)-pyridineHMDB
1'-Oxide nicotineHMDB
1-Methyl-2-(3-pyridyl)pyrrolidine 1-oxideHMDB
N-Oxide 3-(1-methyl-2-pyrrolidinyl)pyridineHMDB
Nicotine 1'-oxideHMDB
Nicotine n'-oxideHMDB
Nicotine N(1')-oxideHMDB
Nicotine 1-N-oxide, (R)-isomerHMDB
Nicotine 1-N-oxide, dihydrochloride, (S)-isomerHMDB
Nicotine 1-N-oxide, (1S-cis)-isomerHMDB
Nicotine 1-N-oxide, (1S-trans)-isomerHMDB
Nicotine 1-N-oxide, (2S)-isomerHMDB
Nicotine 1-N-oxide, 14C-labeled CPDHMDB
Nicotine 1-N-oxide, dihydrochloride, (1S-trans)-isomerHMDB
Nicotine 1-N-oxide, (1R-cis)-isomerHMDB
Nicotine 1-N-oxide, (1R-trans)-isomerHMDB
Nicotine 1-N-oxide, (S)-isomerHMDB
Nicotine 1-N-oxide, dihydrochloride, (1R-trans)-isomerHMDB
Chemical FormulaC10H14N2O
Average Molecular Weight178.231
Monoisotopic Molecular Weight178.11061308
IUPAC Name1-methyl-2-(pyridin-3-yl)pyrrolidin-1-ium-1-olate
Traditional Namenicotine 1-N-oxide
CAS Registry Number63551-14-4
InChI Identifier
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
  • Pyrrolidinylpyridine
  • Alkaloid or derivatives
  • N-alkylpyrrolidine
  • Trialkyl amine oxide
  • Heteroaromatic compound
  • Pyrrolidine
  • Azacycle
  • N-oxide
  • Trisubstituted n-oxide
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic zwitterion
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Route of exposure:


Biological location:


Naturally occurring process:


Biological role:

Physical Properties
Experimental Properties
Melting Point-79 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1000 mg/mLNot Available
LogP1.17HANSCH,C ET AL. (1995)
Predicted Properties
Water Solubility11.6 g/LALOGPS
pKa (Strongest Basic)4.74ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.77 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity51.7 m³·mol⁻¹ChemAxon
Polarizability19.19 ųChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0f96-8900000000-b2b7dd335c3a05aa57bbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-c5515911fcd12c368c31Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004l-5900000000-c464534b639004ad3b54Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uec-9300000000-2a2d1afce79d8998d3b3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-4f451a2d6c2540a25c95Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0900000000-7b621173e20fa3dd7ce0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fb9-7900000000-1d685bcb46ea923561a3Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Adrenal Medulla
  • Bladder
  • Brain
  • Fetus
  • Fibroblasts
  • Hair
  • Kidney
  • Liver
  • Lung
  • Mouth
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Skeletal Muscle
  • Skin
  • Stratum Corneum
  • Testes
Normal Concentrations
BloodExpected but not Quantified Not AvailableNot AvailableNormal
    UrineExpected but not Quantified Not AvailableNot AvailableNormal
      Abnormal Concentrations
      Not Available
      Associated Disorders and Diseases
      Disease ReferencesNone
      Associated OMIM IDsNone
      DrugBank IDNot Available
      Phenol Explorer Compound IDNot Available
      FoodDB IDFDB022656
      KNApSAcK IDNot Available
      Chemspider ID396
      KEGG Compound IDNot Available
      BioCyc IDNot Available
      BiGG IDNot Available
      Wikipedia LinkNot Available
      METLIN IDNot Available
      PubChem Compound409
      PDB IDNot Available
      ChEBI ID30734
      Food Biomarker OntologyNot Available
      VMH IDNot Available
      Synthesis ReferenceNot Available
      Material Safety Data Sheet (MSDS)Not Available
      General References
      1. Court JA, Johnson M, Religa D, Keverne J, Kalaria R, Jaros E, McKeith IG, Perry R, Naslund J, Perry EK: Attenuation of Abeta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking. Neuropathol Appl Neurobiol. 2005 Oct;31(5):522-35. [PubMed:16150123 ]
      2. LeSage MG, Keyler DE, Pentel PR: Current status of immunologic approaches to treating tobacco dependence: vaccines and nicotine-specific antibodies. AAPS J. 2006 Feb 24;8(1):E65-75. [PubMed:16584135 ]
      3. Fang Y, Svoboda KK: Nicotine inhibits myofibroblast differentiation in human gingival fibroblasts. J Cell Biochem. 2005 Aug 15;95(6):1108-19. [PubMed:15962330 ]
      4. Eliasson B, Smith U, Lonnroth P: No acute effects of smoking and nicotine nasal spray on lipolysis measured by subcutaneous microdialysis. Eur J Clin Invest. 1997 Jun;27(6):503-9. [PubMed:9229231 ]
      5. 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. [PubMed:8068568 ]
      6. Tsurutani J, Castillo SS, Brognard J, Granville CA, Zhang C, Gills JJ, Sayyah J, Dennis PA: Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis. 2005 Jul;26(7):1182-95. Epub 2005 Mar 24. [PubMed:15790591 ]
      7. Ramachandran J, Rubenstein D, Bluestein D, Jesty J: Activation of platelets exposed to shear stress in the presence of smoke extracts of low-nicotine and zero-nicotine cigarettes: the protective effect of nicotine. Nicotine Tob Res. 2004 Oct;6(5):835-41. [PubMed:15700919 ]
      8. Miller VM, Lewis DA, Rud KS, Offord KP, Croghan IT, Hurt RD: Plasma nitric oxide before and after smoking cessation with nicotine nasal spray. J Clin Pharmacol. 1998 Jan;38(1):22-7. [PubMed:9597555 ]
      9. Hureiki J, Laqueille X: [The Tuaregs addiction to tea, to smokeless tobacco and to milk: ethnological and clinical approach]. Encephale. 2003 Jan-Feb;29(1):42-8. [PubMed:12640326 ]
      10. Bonci A, Bernardi G, Grillner P, Mercuri NB: The dopamine-containing neuron: maestro or simple musician in the orchestra of addiction? Trends Pharmacol Sci. 2003 Apr;24(4):172-7. [PubMed:12707003 ]
      11. Nadler JL, Velasco JS, Horton R: Cigarette smoking inhibits prostacyclin formation. Lancet. 1983 Jun 4;1(8336):1248-50. [PubMed:6134041 ]
      12. Terry AV Jr, Hernandez CM, Hohnadel EJ, Bouchard KP, Buccafusco JJ: Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition. CNS Drug Rev. 2005 Autumn;11(3):229-52. [PubMed:16389292 ]
      13. Reddy A, Sood A, Rust PF, Busby JE, Varn E, Mathur RS, Mathur S: The effect of nicotine on in vitro sperm motion characteristics. J Assist Reprod Genet. 1995 Mar;12(3):217-23. [PubMed:8520189 ]
      14. Joshi M, Tyndale RF: Regional and cellular distribution of CYP2E1 in monkey brain and its induction by chronic nicotine. Neuropharmacology. 2006 Apr;50(5):568-75. Epub 2005 Dec 20. [PubMed:16368115 ]
      15. Marchei E, Durgbanshi A, Rossi S, Garcia-Algar O, Zuccaro P, Pichini S: Determination of arecoline (areca nut alkaloid) and nicotine in hair by high-performance liquid chromatography/electrospray quadrupole mass spectrometry. Rapid Commun Mass Spectrom. 2005;19(22):3416-8. [PubMed:16259042 ]
      16. Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Muller P, Bachmann MF: A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity. Eur J Immunol. 2005 Jul;35(7):2031-40. [PubMed:15971275 ]
      17. Lerman C, Tyndale R, Patterson F, Wileyto EP, Shields PG, Pinto A, Benowitz N: Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther. 2006 Jun;79(6):600-8. Epub 2006 May 11. [PubMed:16765148 ]
      18. Lambers DS, Clark KE: The maternal and fetal physiologic effects of nicotine. Semin Perinatol. 1996 Apr;20(2):115-26. [PubMed:8857697 ]
      19. Hansson L, Choudry NB, Karlsson JA, Fuller RW: Inhaled nicotine in humans: effect on the respiratory and cardiovascular systems. J Appl Physiol (1985). 1994 Jun;76(6):2420-7. [PubMed:7928866 ]
      20. Warner DO, Joyner MJ, Charkoudian N: Nicotine increases initial blood flow responses to local heating of human non-glabrous skin. J Physiol. 2004 Sep 15;559(Pt 3):975-84. Epub 2004 Jul 22. [PubMed:15272048 ]