Nicotine racemate
2D structure of nicotine as a racemic mixture
3D structure of (R)-nicotine
3D structure of (S)-nicotine
Synonyms Nikotin
Brand names Nicabate, Nicorette and others

IUPAC name
IUPAC name
Clinical information
Preg. cat.
Legal status
AU: Pharmacy Medicine (S2)
Routes Inhalation, insufflation, buccal, sublingual, transdermal

Salts Polacrilex, resinate, tartrate
ATC code N07BA01
ChemSpider 917
DrugBank DB00184
PubChem 942
MedlinePlus 000953
MeSH ID D009538
1UW6 (RCSB, PDBe; X-ray)
External links
DailyMed nicotine search international, monograph
Jmol See Jmol subpages
Licensing data US FDA: link.
MSR monograph
emc nicotine search
TGA-eBS nicotine search
Chemical properties
Formula C10H14N2
Mol. mass
Mol. mass for MFs
162.2316 g/mol

Nicotine is the chief psychoactive constituent found within tobacco (Nicotiana tabacum) and is a parasympathomimetic,[note 1] unlike the other major strong stimulants the amfetamines, cathinones and cocaine which are all sympathomimetic agents.[note 2] It primarily acts by binding to subunits of the nicotinic acetylcholine receptors, especially in the mesolimbic pathway of the brain where they facilitate dopamine release, causing reward and hence addiction. Although other chemical constituents of tobacco smoke, such as the harmala alkaloids, also contribute to the addictive effects of tobacco smoking, nicotine is generally considered the most important of its constituents to the development of an addiction to tobacco smoking. Approximately six million people die, worldwide, each year from tobacco smoking, of which some 200,000 are in children.[1]

It is unique amongst stimulants as when it is administered via the usual way (that is, in cigarettes) it is nigh impossible to overdose on it. The reason why is that an average cigarette administers approximately 1-3 mg of nicotine and the estimated fatal dose for adults is 60 mg for non-smokers, 120 mg for smokers and consequently it is simply impractical to OD on cigarettes alone.[2] It is usually administered via inhalation, in the form of tobacco smoke. It lacks significant oral bioavailability due to extensive first-pass metabolism in the liver and hence eating tobacco products usually does not possess any real potential for causing toxicity. There are over 4,000 different compounds in tobacco smoke, of which over 250 are known to be harmful and over 50 are known to cause cancer.[3]

It usually administered via one of three routes: buccal[note 3], inhalation[note 4] or transdermal[note 5].[2][4]

Many countries have implemented smoke-free policies, which are basically where it is illegal to smoke in public places like restaurants and alike, this is designed to reduce the prevalence of complications from second-hand smoke, especially in children.[5] The first country to do this was Australia.[5]

Medical useEdit

While any therapeutic benefit obtained from nicotine consumption would not surpass the detrimental consequences of smoking on one’s health, there is some evidence to suggest that nicotine may be an effective treatment for Parkinson disease (PD) and ulcerative colitis (UC; a form of inflammatory bowel disease).[6][7] There is also some evidence of benefits on the negative (that is, how it affects one's ability to experience pleasure, have motivation to do things, etc.) and cognitive symptoms (like inattention, short-term memory problems, difficulties with decision-making, processing speed, etc.) of schizophrenia.[8]

Short-term effects of nicotineEdit

In plants it serves as an herbicide, that is, a compound that kills off herbivores that eat the plant. This is because higher doses cause blockade of the neuromuscular junction (leading to respiratory arrest) and can provoke seizures. Lower doses produce typical stimulant effects such as: slight increases in heart rate, blood pressure and respiratory rate, increased energy, improved ability to concentrate, improved memory and recall, reduced appetite, nausea, reduced fatigue, erectile dysfunction, reduced fertility in both sexes and an increase sense of well-being.[9]

It is also unusual in that, in the short-term tobacco smoking produces minimal ill effects, but in the long-term it causes real problems.[9]

Long-term consequences of tobacco abuseEdit

The major causes of tobacco-related morbidity (injury/disease) and mortality (death) are (with the fold increase in rates of these diseases caused by smoking listed in brackets; the % of cases, worldwide, that could be attributed to smoking are also listed in brackets):[10] ischaemic heart disease (13% [Australia]), peripheral vascular disease, strokes, aneurysm, tuberculosis, diabetes mellitus, ectopic pregnant, rheumatoid arthritis, lung cancer (5-10x; 80%), chronic obstructive pulmonary disease, pneumonia, cataracts, hip fractures, macular degeneration and miscellaneous other cancers, including: acute myeloid leukaemia, bladder cancer (2-3x; 40-70%), bowel cancer, breast cancer, cervical cancer, kidney cancer, laryngeal cancer (12x), oesophageal cancer, oropharyngeal cancer (throat/mouth cancer; 27x), pancreatic cancer (30%) and stomach cancer.[11]:5[12]

Second-hand smoke exposure can cause or exacerbate: asthma, lower respiratory tract infections, lung cancer and ischaemic heart disease.[3] Occasional smoking (like once off smokes) are at a higher risk for developing ischaemic heart disease (this risk is considered virtually identical to that of a frequent smoker) and lung cancer.[13]

Despite its mountain of negative effects there is some evidence that smokers may have a lower risk of developing Parkinson disease in the future, consequently nicotine has been tried as a potential treatment for Parkinson disease with some signs of efficacy.[6] Likewise, ulcerative colitis is known to be less common in smokers and smoking seems to ameloriate the symptoms and progression of the disease.[7]

Mechanism of actionEdit

Acts via activating the nicotinic acetylcholine receptors (nAChRs), especially the neuronal and adrenal subtypes: in the mesolimbic circuits it induces the release of dopamine via the α4β2 and α6β2 subtypes (producing euphoria and addiction),[14] whereas in the adrenal medulla the α3β4 receptor predominates. The α7 nAChR is believed to be responsible for the pro-cognitive effects of nicotine.[15] The major varieties found in the human brain are: α7, α3β4 and α4β2.[15] They influence the release of the following neurotransmitters: acetylcholine, serotonin, noradrenaline, γ-aminobutyric acid (GABA), glutamate and the endorphins.[9]:124-136[15] Tobacco smoke also inhibits monoamine oxidase, which could potentiate the monoaminergic effects of nicotine, including the euphoria it produces.[16]

Whereas the α3β4 is involved in the cardiovascular effects of nicotine.[15] In the kidneys the α7 subunit predominates.[17] This means that smoking can accelerate the progression of chronic kidney disease.[17] The nAChRs (specifically the α7 subunit) also promote angiogenesis, the process by which cancers migrate and grow stronger.[18]

Fatty acid amide hydrolase (the enzyme that catalyses the breakdown of anandamide) has also been implicated in nicotine dependence.[19]



Cotinine's 2D structure


Nicotine-N-oxide's 2D structure

Its elimination half-life is 1-2 hours and is metabolized chiefly via CYP2A6 to cotinine (an active metabolite, but it is a much weaker stimulant and has a significantly longer half-life of 12-19 hours, it is the major way how physicians and sports authorities can test for recent tobacco use) and nicotine-N-oxide.[20][21] Tobacco induces[note 6] CYP1A2 and CYP2B6, hence it is known to reduce the levels of various medications including antipsychotics (including clozapine), antidepressants (mostly the older antidepressants, the so called "tricyclic antidepressants"), caffeine, β-blockers, oestrogens, insulin, theophylline (a drug for asthma) and pentazocine (a painkiller).[22]

It is, in its freebase form, a colourless or pale yellow, oily liquid at room temperature that is miscible with water, highly soluble in most organic solvents and reacts upon contact with air.[4] Tobacco leaves contain between 0.5% and 8% nicotine, mostly as malate or citrate salts.[4] It is also found in other nightshade plants such as potato, eggplant and tomato plants, including in the fruit/vegetables we eat.[23] Likewise there are a number of other related compounds in various plants including the ones we eat.[24][25]

Tobacco smoke also contains acetaldehyde (which is also believed to be responsible for the cancer-causing effects of alcohol), benzene (the cancer-causing chemical found in petrol and diesel) and the harmala alkaloids which includes two alkaline substances, harman and norharman, both of which reversibly inhibit MAOA and as MAOA degrades dopamine in the CNS this could potentially potentiate the rewarding (that is, pleasurable) effects of nicotine.[24][26][27] It also inhibits MAOB.[28]

Another closely-related naturally-occurring compound to nicotine that activates the nAChRs is called cytisine.

Nicotine-related alkaloids

Alkaloids chemically related to nicotine


Nicotine racemate
200px (R)-nicotine
200px (S)-nicotine


  1. Meaning it activates the "rest and digest" division of the autonomic nervous system; the part of the nervous system that regulates our involuntary movements, like the ones that keep our bowels moving.
  2. That is, they activate the "fight or flight" response in the body
  3. That is, via chewing gum or tobacco
  4. That is, via smoking or via an e-cigarette
  5. That is via nicotine patches
  6. Which means it increases the activity of this enzyme

External linksEdit

Reference listEdit

  1. World Health Organization (May 2014). "Tobacco". Media Centre. Geneva, Switzerland: World Health Organization. Retrieved 3 August 2014. 
  2. 2.0 2.1 Brunton, LL; Chabner, BA; Knollmann, BC, ed. (2010). Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill Professional. ISBN 978-0-07-162442-8. 
  3. 3.0 3.1 World Health Organization. "10 FACTS ON SECOND-HAND SMOKE". Fact File. World Health Organization. Retrieved 4 August 2014. 
  4. 4.0 4.1 4.2 Brayfield, A, ed. (13 December 2013). "Nicotine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 1 August 2014. 
  5. 5.0 5.1 WHO (2013). WHO REPORT ON THE GLOBAL TOBACCO EPIDEMIC, 2013 Enforcing bans on tobacco advertising, promotion and sponsors (PDF). Geneva, Switzerland: World Health Organization. ISBN 978-92-4-069160-5. 
  6. 6.0 6.1 Quik, M; Perez, XA; Bordia, T (July 2012). "Nicotine as a potential neuroprotective agent for Parkinson's disease.". Movement Disorders 27 (8): 947–57. PMC 3685410. PMID 22693036. doi:10.1002/mds.25028. 
  7. 7.0 7.1 Lunney, PC; Leong, RW (December 2012). "Review article: Ulcerative colitis, smoking and nicotine therapy.". Alimentary Pharmacology & Therapeutics 36 (11-12): 997–1008. PMID 23072629. doi:10.1111/apt.12086. 
  8. Herman, AI; Sofuoglu, M (July 2010). "Cognitive effects of nicotine: genetic moderators.". Addiction Biology 15 (3): 250–65. PMC 2903639. PMID 20456288. doi:10.1111/j.1369-1600.2010.00213.x. 
  9. 9.0 9.1 9.2 U.S. Department of Health and Human Services (2010). How Tobacco Smoke Causes Disease The Biology and Behavioral Basis for Smoking-Attributable Disease A Report of the Surgeon General. Atlanta, USA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. ISBN 978-0-16-084078-4. 
  10. World Health Organization. "Cancer". Tobacco Free Initiative. Genever, Switzerland: World Health Organization. Retrieved 3 August 2014. 
  11. U.S. Department of Health and Human Services (2014). The Health Consequences of Smoking—50 Years of Progress A Report of the Surgeon General. Atlanta, USA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 
  12. Lee, J; Cooke, JP (November 2012). "Nicotine and pathological angiogenesis.". Life Sciences 91 (21-22): 1058–64. PMC 3695741. PMID 22796717. doi:10.1016/j.lfs.2012.06.032. 
  13. Schane, RE; Ling, PM; Glantz, SA (April 2010). "Health effects of light and intermittent smoking: a review.". Circulation 121 (13): 1518–22. PMC 2865193. PMID 20368531. doi:10.1161/CIRCULATIONAHA.109.904235. 
  14. Wu, J; Gao, M; Shen, JX; Shi, WX; Oster, AM; Gutkin, BS (October 2013). "Cortical control of VTA function and influence on nicotine reward.". Biochemical Pharmacology 86 (8): 1173–80. PMID 23933294. doi:10.1016/j.bcp.2013.07.013. 
  15. 15.0 15.1 15.2 15.3 Benowitz, NL (2009). "Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.". Annual Review of Pharmacology and Toxicology 49: 57–71. PMC 2946180. PMID 18834313. doi:10.1146/annurev.pharmtox.48.113006.094742. 
  16. Fowler, JS; Logan, J; Wang, GJ; Volkow, ND (January 2003). "Monoamine oxidase and cigarette smoking.". Neurotoxicology 24 (1): 75–82. PMID 12564384. doi:10.1016/S0161-813X(02)00109-2. 
  17. 17.0 17.1 Jain, G; Jaimes, EA (October 2013). "Nicotine signaling and progression of chronic kidney disease in smokers.". Biochemical Pharmacology 86 (8): 1215–23. PMID 23892062. doi:10.1016/j.bcp.2013.07.014. 
  18. Lee, J; Cooke, JP (November 2012). "Nicotine and pathological angiogenesis.". Life Sciences 91 (21-22): 1058–64. PMC 3695741. PMID 22796717. doi:10.1016/j.lfs.2012.06.032. 
  19. Muldoon, PP; Lichtman, AH; Parsons, LH; Damaj, MI (2013). "The role of fatty acid amide hydrolase inhibition in nicotine reward and dependence". Life Sciences 92 (8-9): 458–462. ISSN 0024-3205. PMC 3477273. PMID 22705310. doi:10.1016/j.lfs.2012.05.015. 
  20. Montalto, NJ; Wells, WO; Jones, GW (September 2007). "Validation of self-reported smoking status using saliva cotinine: a rapid semiquantitative dipstick method.". Cancer Epidemiology, Biomarkers & Prevention 16 (9): 1858–62. PMID 17855706. doi:10.1158/1055-9965.EPI-07-0189. 
  21. Benowitz, NL (2009). "Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.". Annual Review of Pharmacology and Toxicology 49: 57–71. PMC 2946180. PMID 18834313. doi:10.1146/annurev.pharmtox.48.113006.094742. 
  22. Lucas, C; Martin, J (June 2013). "Smoking and drug interactions". Australian Prescriber 36 (3): 102–104. ISSN 0312-8008. 
  23. Siegmund, B; Leitner, E; Pfannhauser, W (August 1999). "Determination of the nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake.". Journal of Agricultural and Food Chemistry 47 (8): 3113–20. PMID 10552617. doi:10.1021/jf990089w. 
  24. 24.0 24.1 Scientific Committee on Emerging and Newly Identified Health Risks (6 July 2010). "Addictiveness and Attractiveness of Tobacco Additives" (PDF). Directorate-General for Health & Consumers. European Commission. Retrieved 13 June 2014. 
  25. Hukkanen, J; Jacob P, 3rd; Benowitz, NL (March 2005). "Metabolism and disposition kinetics of nicotine.". Pharmacological Reviews 57 (1): 79–115. PMID 15734728. doi:10.1124/pr.57.1.3. 
  26. De Biasi, M; Dani, JA (2011). "Reward, addiction, withdrawal to nicotine.". Annual Review of Neuroscience 34: 105–30. PMC 3137256. PMID 21438686. doi:10.1146/annurev-neuro-061010-113734. 
  27. Hendrickson, LM; Guildford, MJ; Tapper, AR (2013). "Neuronal Nicotinic Acetylcholine Receptors: Common Molecular Substrates of Nicotine and Alcohol Dependence". Frontiers in Psychiatry 4. PMC 3639424. PMID 23641218. doi:10.3389/fpsyt.2013.00029. 
  28. Herraiz, T; Chaparro, C (January 2005). "Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors.". Biochemical and Biophysical Research Communications 326 (2): 378–86. PMID 15582589. doi:10.1016/j.bbrc.2004.11.033.