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"Nicotine is amazing"
{{About|the chemical|other uses|Nicotine (disambiguation)}}
{{Drugbox| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 420440849
| IUPAC_name = 3-[1-Methylpyrrolidin-2-yl]pyridine
| image = Nicotine.svg
| width = 200
| image2 = Nicotine3Dan2.gif
| width2 = 200
| caption =

<!--Clinical data-->
| tradename = Nicorette, Nicotrol
| Drugs.com = {{drugs.com|monograph|nicotine}}
| pregnancy_AU = D
| pregnancy_US = D
| legal_AU = S4
| legal_UK = GSL
| legal_US = OTC
| dependency_liability = High
| routes_of_administration = [[Inhalation]]; [[Insufflation (medicine)|Insufflation]]; [[Oral route|Oral]] &ndash; Buccal, Sublingual, and Ingestion; [[Transdermal]]; [[Suppository|Rectal]],

<!--Pharmacokinetic data-->
| bioavailability = 20 to 45% (oral), 53% (intranasal), 68% (transdermal)
| protein_bound = <5%
| metabolism = [[Hepatic]]
| elimination_half-life = 1-2 hours; 20 hours active metabolite (cotinine)
| excretion = Urine (10-20% (gum), pH-dependent; 30% (inhaled); 10-30% (intranasal))

<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 54-11-5
| ATC_prefix = N07
| ATC_suffix = BA01
| ATC_supplemental = {{ATCvet|P53|AX13}}
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 18723
| PubChem = 89594
| IUPHAR_ligand = 2585
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00184
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 80863
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6M3C89ZY6R
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03365
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 3

<!--Chemical data-->
| C=10 | H=14 | N=2
| molecular_weight = 162.12 g/mol
| smiles = CN(CCC1)[C@@H]1C2=CC=CN=C2
| InChI = 1/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/t10-/m0/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/t10-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SNICXCGAKADSCV-JTQLQIEISA-N
| density = 1.01
| melting_point = -79
| boiling_point = 247
}}
'''Nicotine''' is a [[potency (pharmacology)|potent]] [[parasympathomimetic]] [[alkaloid]] found in the [[nightshade]] family of plants ([[Solanaceae]]) and a [[stimulant]] [[drug]]. It is a [[Nicotinic agonist|nicotinic acetylcholine receptor agonist]]. It [[biosynthesis|is made]] in the roots and accumulates in the leaves of the plants.
It constitutes approximately 0.6–3.0% of the dry weight of [[tobacco]]<ref>{{cite web|url=http://dccps.nci.nih.gov/tcrb/monographs/9/m9_3.PDF |title=Smoking and Tobacco Control Monograph No. 9 |format=PDF |date= |accessdate=2012-12-19}}</ref> and is present in the range of 2–7&nbsp;µg/kg of various edible plants.<ref name="acs">{{cite web |url=http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/1999/47/i08/abs/jf990089w.html |title=Determination of the Nicotine Content of Various Edible Nightshades (Solanaceae) and Their Products and Estimation of the Associated Dietary Nicotine Intake |accessdate=2008-10-05}}</ref>
It functions as an [[plant defense against herbivory|antiherbivore chemical]]; consequently, nicotine was widely used as an [[insecticide]] in the past<ref>{{Cite book
| last = Rodgman
| first = Alan
| last2 = Perfetti
| first2 = Thomas A.
| title = The chemical components of tobacco and tobacco smoke
| place = Boca Raton, FL
| publisher = CRC Press
| year = 2009
| lccn=2008018913
| isbn = 1-4200-7883-6 }}{{page needed|date=December 2013}}
</ref><ref name=Ujvary>{{Cite book
| first = István | last = Ujváry
| contribution = Nicotine and Other Insecticidal Alkaloids
| editor-first = Izuru | editor-last = Yamamoto
| editor2-first = John | editor2-last = Casida
| title = Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor
| pages = 29–69
| publisher = Springer-Verlag
| location = Tokyo
| year = 1999
}}
</ref>
and nicotine analogs such as [[imidacloprid]] are currently widely used.

In smaller doses (an average [[cigarette]] yields about 1&nbsp;mg of absorbed nicotine), the substance acts as a [[stimulant]] in [[mammal]]s, while high amounts (50–100&nbsp;mg) can be harmful.<ref name=inchem>{{cite web|url=http://www.inchem.org/documents/pims/chemical/nicotine.htm#PartTitle:7.%20TOXICOLOGY |title=Nicotine (PIM) |publisher=Inchem.org |date= |accessdate=2012-12-19}}</ref><ref name=overdose>{{cite web | author = Genetic Science Learning Center | title = How Drugs Can Kill | url = http://learn.genetics.utah.edu/content/addiction/drugskill/ }}</ref><ref name=MayerNewLethalDose2013/>
This stimulant effect is likely a major contributing factor to the dependence-forming properties of [[tobacco smoking]], nicotine patches, nicotine gum, nicotine inhalers and liquid nicotine vapourizers.{{Citation needed|date=April 2013}} According to the [[American Heart Association]], nicotine [[substance use disorder|addiction]] has historically been one of the hardest addictions to break, while the pharmacological and behavioral characteristics that determine nicotine addiction are similar to those determining addiction to [[heroin]] and [[cocaine]]. The nicotine content of popular American-brand cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005. This was found for all major market categories of cigarettes.<ref>{{cite journal
| title = Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands, 1997–2005
| journal = Tobacco Control
| volume = 16
| issue = 5
| pages = e5
| year = 2007
| pmid = 17897974
| doi = 10.1136/tc.2006.019695
| author1 = Connolly, G. N
| author2 = Alpert, H. R
| author3 = Wayne, G. F
| author4 = Koh, H
| pmc = 2598548}}</ref>

Research in 2011 found that nicotine inhibits chromatin-modifying enzymes (class I and II [[histone deacetylases]]); this inhibition has been shown to increase the ability of [[cocaine]] to cause an [[addiction]].<ref>{{cite journal |author=Volkow ND |title=Epigenetics of nicotine: another nail in the coughing |journal=Sci Transl Med |volume=3 |issue=107 |pages=107ps43 |date=November 2011 |pmid=22049068 |doi=10.1126/scitranslmed.3003278 |pmc=3492949}}</ref>

==Psychoactive effects==
{{further|Psychoactive drug}}
Nicotine's [[mood (psychology)|mood]]-altering effects are different by report: in particular it is both a stimulant and a relaxant.<ref>{{cite journal |url=http://www.ti.ubc.ca/newsletter/effective-clinical-tobacco-intervention |title= Effective Clinical Tobacco Intervention |journal=Therapeutics Letter |issue=21 |date=September–October 1997 |pages=1–4}}</ref> First causing a release of [[glucose]] from the liver and [[epinephrine]](adrenaline) from the [[adrenal medulla]], it causes [[stimulation]]. Users report feelings of [[relaxation (psychology)|relaxation]], sharpness, [[calmness]], and [[alertness]].<ref>{{cite journal |id={{INIST|1081618}} |last1=Lagrue |first1=Gilbert |last2=Cormier |first2=Anne |month=June |year=2001 |title=Des récepteurs nicotiniques à la dépendance tabagique : Perspectives thérapeutiques |trans_title=From nicotinic receptors to smoking dependence: Therapeutic prospects |language=fr |journal=Alcoologie et addictologie |issn=1620-4522 |volume=23 |issue=2 |pages=39S–42S}}</ref> Like any stimulant, it may very rarely cause the often uncomfortable [[neuropsychiatric]] effect of [[akathisia]]. By reducing the [[appetite]] and raising the [[metabolism]], some smokers may [[weight loss|lose weight]] as a consequence.<ref>{{cite journal |id={{INIST|1081638}} |last1=Orsini |first1=Jean-Claude |month=June |year=2001 |title=Dépendance tabagique et contrôle central de la glycémie et de l'appétit |trans_title=Dependence on tobacco smoking and brain systems controlling glycemia and appetite |language=fr |journal=Alcoologie et addictologie |issn=1620-4522 |volume=23 |issue=2 Suppl |pages=28S–36S}}</ref><ref>{{cite journal |doi=10.1038/sj.npp.1300597 |laysummary=http://archive.uninews.unimelb.edu.au/view-49206.html |laysource=The University of Melbourne |laydate=1 November 2004 |title=Effect of Short-Term Cigarette Smoke Exposure on Body Weight, Appetite and Brain Neuropeptide Y in Mice |year=2004 |last1=Chen |first1=Hui |last2=Vlahos |first2=Ross |last3=Bozinovski |first3=Steve |last4=Jones |first4=Jessica |last5=Anderson |first5=Gary P |last6=Morris |first6=Margaret J |journal=Neuropsychopharmacology}}</ref>

When a [[cigarette]] is smoked, nicotine-rich blood passes from the [[human lung|lung]]s to the [[human brain|brain]] within seven seconds and immediately stimulates the release of many chemical messengers such as [[acetylcholine]], [[norepinephrine]], [[epinephrine]], [[arginine vasopressin]], [[serotonin]], [[dopamine]], and [[beta-endorphin]].<ref>Pomerleau OF, Pomerleau CS (1984). Neuroregulators and the reinforcement of smoking: Towards a biobehavioral explanation. ''Neuroscience and Biobehavioral Reviews'', 8:503-513.</ref> <ref>Pomerleau OF, Rosecrans J (1989). Neuroregulatory effects of nicotine. ''Psychoneuroendocrinology'' 14:407-423.</ref> This release of neurotransmitters and hormones is responsible for most of nicotine's psychoactive effects. Nicotine appears to enhance [[attention|concentration]]<ref name="rusted">{{cite journal |author=Rusted J, Graupner L, O'Connell N, Nicholls C |title=Does nicotine improve cognitive function? |journal=Psychopharmacology (Berl.) |volume=115 |issue=4 |pages=547–9 |date=August 1994 |pmid=7871101 |doi=10.1007/BF02245580}}</ref> and memory due to the increase of [[acetylcholine]]. It also appears to enhance [[alertness]] due to the increases of [[acetylcholine]] and [[norepinephrine]]. [[Arousal]] is increased by the increase of [[norepinephrine]]. [[Pain]] is reduced by the increases of [[acetylcholine]] and beta-endorphin. [[Anxiety]] is reduced by the increase of [[beta-endorphin]]. Nicotine also extends the duration of positive effects of dopamine<ref>{{cite journal |author=Easton, John |title=Nicotine extends duration of pleasant effects of dopamine |journal=The University of Chicago Chronicle|volume=21 |issue=12 |date=March 28, 2002 |url=http://chronicle.uchicago.edu/020328/nicotine.shtml}}</ref> and increases sensitivity in brain reward systems.<ref name=Kenny>{{cite journal |author=Kenny PJ, Markou A |title=Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity |journal=Neuropsychopharmacology |volume=31 |issue=6 |pages=1203–11 |date=Jun 2006 |pmid=16192981 |doi=10.1038/sj.npp.1300905}}</ref> Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.<ref>{{cite web|author=|url=http://www.erowid.org/chemicals/nicotine/nicotine_dose.shtml|title=Erowid Nicotine Vault : Dosage |publisher=Erowid.org |date=2011-10-14 |accessdate=2012-12-19}}</ref>

Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine.<ref>{{cite book |doi=10.1007/978-1-4899-0888-9_9 |chapter=Factors Governing Recruitment to and Maintenance of Smoking |title=Drug and Alcohol Use |year=1989 |last1=Golding |first1=J. F. |last2=Mangan |first2=G. L. |isbn=978-1-4899-0890-2 |pages=101–17 |chapterurl=http://books.google.com/books?id=s9_EWPshR4QC&pg=PA101 |editor1-first=Stanley |editor1-last=Einstein}}</ref> This stimulates [[action potential|nerve transmission]]. When they wish to relax, they take deep puffs, which produce a high level of blood nicotine, which depresses the passage of [[nerve impulses]], producing a mild sedative effect. At low doses, nicotine potently enhances the actions of [[norepinephrine]] and [[dopamine]] in the brain, causing a drug effect typical of those of [[psychostimulants]]. At higher doses, nicotine enhances the effect of [[serotonin]] and [[opiate]] activity, producing a calming, [[analgesic|pain-killing]] effect. Nicotine is unique in comparison to most [[drug]]s, as its profile changes from [[stimulant]] to [[sedative]]/[[pain killer]] in increasing [[dose (biochemistry)|dosage]]s and use, a phenomenon described by Paul Nesbitt in his doctoral dissertation<ref>Nesbitt P (1969). Smoking, physiological arousal, and emotional response. Unpublished doctoral dissertation, Columbia University.</ref> and subsequently referred to as "Nesbitt's Paradox."

==Medical uses==
[[Image:Nicoderm.JPG|thumb|right|A 21 mg patch applied to the left arm. The [[Cochrane Collaboration]] finds that NRT increases a quitter's chance of success by 50 to 70%.<ref name=CD000146>{{cite journal |author=Stead LF, Perera R, Bullen C, Mant D, Lancaster T |title=Nicotine replacement therapy for smoking cessation |journal=Cochrane Database Syst Rev |issue=1 |pages=CD000146 |year=2008 |pmid=18253970 |doi=10.1002/14651858.CD000146.pub3 |editor1-last=Stead |editor1-first=Lindsay F}}</ref> But in 1990, researchers found that 93% of users returned to smoking within six months.<ref>{{cite news|author=Millstone, Ken|title=Nixing the patch: Smokers quit cold turkey|url=http://jscms.jrn.columbia.edu/cns/2007-02-13/millstone-coldturkeyquitters.html|date=February 13, 2007|publisher=Columbia.edu News Service|accessdate=May 23, 2010}}</ref>]]
Although population level effectiveness has not been demonstrated,<ref>{{cite journal |doi=10.1016/j.addbeh.2005.05.054 |title=Smoking status of Australian general practice patients and their attempts to quit |year=2006 |last1=Doran |first1=Christopher M. |last2=Valenti |first2=Lisa |last3=Robinson |first3=Maxine |last4=Britt |first4=Helena |last5=Mattick |first5=Richard P. |journal=Addictive Behaviors |volume=31 |issue=5 |pages=758–66 |pmid=16137834}}</ref><ref>{{citation|author=Gallup Poll|title=Most U.S. Smokers Want to Quit, Have Tried Multiple Times|url=http://www.gallup.com/poll/163763/smokers-quit-tried-multiple-times.aspx|date=July 31, 2013|publisher=Gallup|accessdate=December 17, 2013}}</ref><ref>{{cite journal |doi=10.1146/annurev-publhealth-031811-124624 |title=Quitlines and Nicotine Replacement for Smoking Cessation: Do We Need to Change Policy? |year=2012 |last1=Pierce |first1=John P. |last2=Cummins |first2=Sharon E. |last3=White |first3=Martha M. |last4=Humphrey |first4=Aimee |last5=Messer |first5=Karen |journal=Annual Review of Public Health |volume=33 |pages=341–56 |pmid=22224888}}</ref> the primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate [[smoking]] with the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence.

However, in a few situations, smoking has been observed to be of therapeutic value.
These are often referred to as "[[Smoker’s Paradoxes]]".<ref name="Cohen_2001">{{cite journal | author = Cohen DJ, Doucet M, Cutlip DE, Ho KK, Popma JJ, Kuntz RE | title = Impact of smoking on clinical and angiographic restenosis after percutaneous coronary intervention: another smoker's paradox? | journal = Circulation | volume = 104 | issue = 7 | pages = 773–8 |date=August 2001 | pmid = 11502701 | doi = 10.1161/hc3201.094225 }}</ref> Although in most cases the actual mechanism is understood only poorly or not at all, it is generally believed that the principal beneficial action is due to the nicotine administered, and that administration of nicotine without smoking may be as beneficial as smoking, without the higher risk to health due to [[tar (tobacco residue)|tar]] and other substances found in tobacco.

For instance, studies suggest that smokers require less frequent repeated [[revascularization]] after [[percutaneous coronary intervention]](PCI).<ref name="Cohen_2001"/> Risk of [[ulcerative colitis]] has been frequently shown to be reduced by smokers on a dose-dependent basis; the effect is eliminated if the individual stops smoking.<ref name="ohcm">{{cite book |author=Longmore, M., Wilkinson, I., Torok, E. |title=Oxford Handbook of Clinical Medicine |page=232 |edition=5th}}</ref><ref name="pmid11069313">{{cite journal | author = Green JT, Richardson C, Marshall RW, Rhodes J, McKirdy HC, Thomas GA, Williams GT | title = Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis | journal = Aliment. Pharmacol. Ther. | volume = 14 | issue = 11 | pages = 1429–34 |date=November 2000 | pmid = 11069313 | doi = 10.1046/j.1365-2036.2000.00847.x }}</ref> Smoking also appears to interfere with development of [[Kaposi's sarcoma]] in patients with HIV.<ref name="pmid12441327">{{cite journal | author = Goedert JJ, Vitale F, Lauria C, Serraino D, Tamburini M, Montella M, Messina A, Brown EE, Rezza G, Gafà L, Romano N | title = Risk factors for classical Kaposi's sarcoma | journal = J. Natl. Cancer Inst. | volume = 94 | issue = 22 | pages = 1712–8 |date=November 2002 | pmid = 12441327 | doi = 10.1093/jnci/94.22.1712 |laysummary=http://www.data-yard.net/10b/kaposi.htm |laysource=United Press International |laydate=March 29, 2001}}</ref>

Nicotine reduces the chance of [[preeclampsia]],<ref name="pmid10561644">{{cite journal | author = Lain KY, Powers RW, Krohn MA, Ness RB, Crombleholme WR, Roberts JM | title = Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure | journal = Am. J. Obstet. Gynecol. | volume = 181 | issue = 5 Pt 1 | pages = 1192–6 |date=November 1999 | pmid = 10561644 | doi = 10.1016/S0002-9378(99)70107-9 }}</ref> and [[atopy|atopic disorder]]s such as [[allergic asthma]].<ref name="pmid11422156">{{cite journal | author = Hjern A, Hedberg A, Haglund B, Rosén M | title = Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents |journal = Clin. Exp. Allergy | volume = 31 | issue = 6 | pages = 908–14 |date=June 2001 | pmid = 11422156 | doi = 10.1046/j.1365-2222.2001.01096.x }}</ref>{{dubious|date=March 2013}} A plausible mechanism of action in these cases may be nicotine acting as an [[inflammation|anti-inflammatory agent]], and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects.<ref name=sciam>{{cite journal | author = Melton L | title=Body Blazes | journal=Scientific American |date=June 2006 |pmid=16711354|bibcode=2006SciAm.294f..24M |volume=294 |doi=10.1038/scientificamerican0606-24 |issue=6 | pages = 24 }}</ref>

Tobacco smoke has been shown to contain compounds capable of inhibiting [[monoamine oxidase]], which is responsible for the degradation of dopamine in the human brain. When dopamine is broken down by MAO-B, neurotoxic by-products are formed, possibly contributing to Parkinson's and Alzheimers disease.<ref name="pmid10942038">{{cite journal | author = Fratiglioni L, Wang HX | title = Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies | journal = Behav. Brain Res. | volume = 113 | issue = 1–2 | pages = 117–20 |date=August 2000 | pmid = 10942038 | doi = 10.1016/S0166-4328(00)00206-0 }}</ref>

While tobacco smoking is associated with an increased risk of Alzheimer's disease,<ref name="pmid19105840">{{cite journal|author=Peters R, Poulter R, Warner J, Beckett N, Burch L, Bulpitt C |title=Smoking, dementia and cognitive decline in the elderly, a systematic review |journal=BMC Geriatr |volume=8 |page=36 |year=2008 |pmid=19105840 |pmc=2642819 |doi=10.1186/1471-2318-8-36 }}</ref> there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease.<ref name="pmid19184661">{{cite journal |author=Henningfield JE, Zeller M |title=Nicotine psychopharmacology: policy and regulatory |journal=Handb Exp Pharmacol |pages=511–34 |year=2009 |pmid=19184661|doi=10.1007/978-3-540-69248-5_18 |series=Handbook of Experimental Pharmacology |isbn=978-3-540-69246-1 |volume=192 |issue=192 }}</ref>
Nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans.<ref>{{cite journal |doi=10.1111/j.1471-4159.2006.04078.x |laysummary=http://www.webmd.com/parkinsons-disease/news/20060811/nicotine-slows-parkinsons-disease |laysource=WebMD |laydate=August 11, 2006 |title=Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates |year=2006 |last1=Quik |first1=Maryka |last2=Parameswaran |first2=Neeraja |last3=McCallum |first3=Sarah E. |last4=Bordia |first4=Tanuja |last5=Bao |first5=Shanshan |last6=McCormack |first6=Alison |last7=Kim |first7=Amy |last8=Tyndale |first8=Rachel F. |last9=Langston |first9=J. William |last10=Di Monte |first10=Donato A. |journal=Journal of Neurochemistry |volume=98 |issue=6 |pages=1866–75 |pmid=16882311}}</ref><ref>{{cite journal |doi=10.1212/01.wnl.0000225050.57553.6d |laysummary=http://www.nutraingredients.com/Research/More-vitamin-B6-linked-to-lower-Parkinson-s-risk |laysource=NutraIngredients |laydate=August 2, 2006 |title=Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease |year=2006 |last1=De Lau |first1=L.M.L. |last2=Koudstaal |first2=P. J. |last3=Witteman |first3=J. C.M. |last4=Hofman |first4=A. |last5=Breteler |first5=M. M.B. |journal=Neurology |volume=67 |issue=2 |pages=315–8 |pmid=16864826}}</ref><ref>{{cite journal |doi=10.1002/ana.21203 |laysummary=http://www.reuters.com/article/2007/10/24/us-parkinsons-nicotine-idUSN2431402020071024 |laysource=Reuters |laydate=October 24, 2007 |title=Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys |year=2007 |last1=Quik |first1=Maryka |last2=Cox |first2=Heather |last3=Parameswaran |first3=Neeraja |last4=O'Leary |first4=Kathryn |last5=Langston |first5=J. William |last6=Di Monte |first6=Donato |journal=Annals of Neurology |volume=62 |issue=6 |pages=588–96 |pmid=17960553}}</ref> A study has shown a protective effect of nicotine itself on neurons due to nicotine activation of α7-nAChR and the PI3K/Akt pathway which inhibits [[apoptosis-inducing factor]] release and mitochondrial translocation, [[cytochrome c]] release and [[caspase 3]] activation.<ref>{{cite journal |author=Yu W, Mechawar N, Krantic S, Quirion R |title=α7 Nicotinic receptor activation reduces β-amyloid-induced apoptosis by inhibiting caspase-independent death through phosphatidylinositol 3-kinase signaling |journal=J. Neurochem. |volume=119 |issue=4 |pages=848–58 |date=November 2011 |pmid=21884524 |doi=10.1111/j.1471-4159.2011.07466.x }}</ref>

Studies have indicated that nicotine can be used to help adults suffering from [[autosomal dominant nocturnal frontal lobe epilepsy]]. The same areas that cause seizures in that form of [[epilepsy]] are responsible for processing nicotine in the brain.<ref>{{cite journal |doi=10.1046/j.1528-1157.2003.11903.x |title=Nicotine as an Antiepileptic Agent in ADNFLE: An N-of-One Study |year=2003 |last1=Willoughby |first1=John O. |last2=Pope |first2=Kenneth J. |last3=Eaton |first3=Vaughn |journal=Epilepsia |volume=44 |issue=10 |pages=1363}}</ref>

Studies suggest a correlation between smoking and [[schizophrenia]], with estimates near 75% for the proportion of schizophrenic patients who smoke. Although the nature of this association remains unclear, it has been argued that the increased level of smoking in schizophrenia may be due to a desire to [[self-medication|self-medicate]] with nicotine.<ref>{{cite journal |author=de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ|title=Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital |journal=Schizophr Res. |volume=56 |issue=1–2|pages=55–65 |date=Jul 2002 |pmid=12084420 |doi=10.1016/S0920-9964(01)00192-X}}</ref><ref>{{cite journal |author=de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM|title=Schizophrenia and smoking: an epidemiological survey in a state hospital |journal=Am J Psychiatry |volume=152 |issue=3 |pages=453–5|date=Mar 1995 |pmid=7864277 |url=http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=7864277}}</ref> Other research found that mildly dependent users got some benefit from nicotine, but not those who were highly dependent.<ref>{{cite journal |author=Aguilar MC, Gurpegui M, Diaz FJ, de Leon J |title=Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions |journal=Br J Psychiatry|volume=186 |issue= 3|pages=215–21 |date=Mar 2005 |pmid=15738502 |doi=10.1192/bjp.186.3.215 }}</ref>

Research at [[Duke University]] Medical Center found that nicotine may improve the symptoms of depression.<ref>{{cite journal |doi=10.1007/s00213-006-0516-y |laysummary=http://www.dukehealth.org/health_library/news/9863 |laysource=Duke Medicine News and Communications |laydate=September 12, 2006 |title=Transdermal nicotine attenuates depression symptoms in nonsmokers: A double-blind, placebo-controlled trial |year=2006 |last1=McClernon |first1=F. Joseph |last2=Hiott |first2=F. Berry |last3=Westman |first3=Eric C. |last4=Rose |first4=Jed E. |last5=Levin |first5=Edward D. |journal=Psychopharmacology |volume=189 |pages=125–33 |pmid=16977477 |issue=1}}</ref>
Nicotine appears to improve [[ADHD]] symptoms. Some studies have focused on benefits of nicotine therapy in adults with ADHD.<ref>{{cite web|url=http://adam.about.com/reports/000030_1.htm|title=Attention-Deficit Hyperactivity Disorder|accessdate=21 September 2009}}</ref>

While acute/initial nicotine intake causes activation of nicotine receptors, chronic low doses of nicotine use leads to desensitisation of nicotine receptors (due to the development of tolerance) and results in an antidepressant effect, with research showing low dose nicotine patches being an effective treatment of [[major depressive disorder]] in non-smokers.<ref name="pmid20965579">{{cite journal |author=Mineur YS, Picciotto MR |title=Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis |journal=Trends Pharmacol. Sci. |volume=31|issue=12 |pages=580–6 |date=December 2010 |pmid=20965579 |pmc=2991594 |doi=10.1016/j.tips.2010.09.004 }}</ref>

Nicotine (in the form of chewing gum or a transdermal patch) has been explored as an experimental treatment for [[OCD]]. Small studies show some success, even in otherwise treatment-refractory cases.<ref name="pmid15610960">{{cite journal |author=Pasquini M, Garavini A, Biondi M|title=Nicotine augmentation for refractory obsessive-compulsive disorder. A case report |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry|volume=29 |issue=1 |pages=157–9 |date=January 2005 |pmid=15610960 |doi=10.1016/j.pnpbp.2004.08.011 }}</ref><ref name="pmid15610934">{{cite journal |author=Lundberg S, Carlsson A, Norfeldt P, Carlsson ML |title=Nicotine treatment of obsessive-compulsive disorder |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=28 |issue=7 |pages=1195–9 |date=November 2004 |pmid=15610934|doi=10.1016/j.pnpbp.2004.06.014 }}</ref><ref name="pmid11822995">{{cite journal |author=Tizabi Y, Louis VA, Taylor CT, Waxman D, Culver KE, Szechtman H |title=Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder|journal=Biol. Psychiatry |volume=51 |issue=2 |pages=164–71 |date=January 2002 |pmid=11822995 |doi= 10.1016/S0006-3223(01)01207-0}}</ref>

The relationship between smoking and inflammatory bowel disease has been firmly established, but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease.<ref>{{cite journal |author=Thomas GA, Rhodes J, Green JT, Richardson C |title=Role of smoking in inflammatory bowel disease: implications for therapy|journal=Postgrad Med J |volume=76 |issue=895 |pages=273–9 |date=May 2000 |pmid=10775279 |pmc=1741576 |doi=10.1136/pmj.76.895.273}}</ref><ref>{{cite journal |author=Rubin DT, Hanauer SB|title=Smoking and inflammatory bowel disease |journal=Eur J Gastroenterol Hepatol |volume=12 |issue=8 |pages=855–62 |date=August 2000|pmid=10958212 |doi=10.1097/00042737-200012080-00004 }}</ref>

==Side effects==
[[File:Side effects of nicotine.svg|thumb|280px|Possible side effects of nicotine.{{Citation needed|date=September 2013}}]]
Nicotine increases blood pressure and heart rate in humans.<ref name="pmid10976548">{{cite journal | author = Sabha M, Tanus-Santos JE, Toledo JC, Cittadino M, Rocha JC, Moreno H | title = Transdermal nicotine mimics the smoking-induced endothelial dysfunction | journal = Clin. Pharmacol. Ther. | volume = 68 | issue = 2 | pages = 167–74 |date=August 2000 | pmid = 10976548 | doi = 10.1067/mcp.2000.108851 }}</ref> Nicotine can also induce potentially atherogenic genes in human coronary artery endothelial cells.<ref name="pmid11166759">{{cite journal | author = Zhang S, Day I, Ye S | title = Nicotine induced changes in gene expression by human coronary artery endothelial cells | journal = Atherosclerosis | volume = 154 | issue = 2 | pages = 277–83 |date=February 2001 | pmid = 11166759 | doi =10.1016/S0021-9150(00)00475-5 }}</ref> Microvascular injury can result through its action on nicotinic acetylcholine receptors (nAChRs).<ref name="pmid11830264">{{cite journal | author = Hawkins BT, Brown RC, Davis TP | title = Smoking and ischemic stroke: a role for nicotine? | journal = Trends Pharmacol. Sci. | volume = 23 | issue = 2 | pages = 78–82 |date=February 2002 | pmid = 11830264 | doi = 10.1016/S0165-6147(02)01893-X }}</ref>

A study on rats showed that nicotine exposure abolishes the beneficial and protective effects of estrogen on the hippocampus,<ref name="pmid19442878">{{cite journal | author = Raval AP, Bhatt A, Saul I | title = Chronic nicotine exposure inhibits 17beta-estradiol-mediated protection of the hippocampal CA1 region against cerebral ischemia in female rats | journal = Neurosci. Lett. | volume = 458 | issue = 2 | pages = 65–9 |date=July 2009 | pmid = 19442878 | doi = 10.1016/j.neulet.2009.04.021 }}</ref> an estrogen-sensitive region of the brain involved in memory formation and retention.

==Dependence and withdrawal==
{{See also|Smoking cessation}}
Modern [[research]] shows that nicotine acts on the brain to produce a number of effects. Specifically, research examining its addictive nature has been found to show that nicotine activates the [[mesolimbic pathway]] ("reward system")&nbsp;– the circuitry within the brain that regulates feelings of pleasure and euphoria.<ref>{{cite book |author=National Institute on Drug Abuse |chapter=Extent, Impact, Delivery, and Addictiveness|chapterurl=http://www.drugabuse.gov/publications/research-reports/tobacco-addiction/what-are-extent-impact-tobacco-use |title=Tobacco Addiction|publisher=National Institutes of Health |location=Bethesda MA |date=June 2009 |series=NIDA Report Research Series |id=09-4342|url=http://www.drugabuse.gov/publications/research-reports/tobacco-addiction}}</ref>

[[Dopamine]] is one of the key [[neurotransmitters]] actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be as addictive as [[cocaine]] and [[heroin]] when used in the form of tobacco.<ref>{{cite news|url=http://www.nytimes.com/1994/08/02/science/is-nicotine-addictive-it-depends-on-whose-criteria-you-use.html | work=The New York Times |first=Philip J. | last=Hilts | title=Is Nicotine Addictive? It Depends on Whose Criteria You Use | date=1994-08-02}}</ref><ref>{{cite news|url=http://www.nytimes.com/1987/03/29/magazine/nicotine-harder-to-kickthan-heroin.html | work=The New York Times | first=Sandra | last=Blakeslee |title=Nicotine: Harder to Kick...Than Heroin | date=1987-03-29}}</ref><ref>{{cite web|url=http://www1.umn.edu/perio/tobacco/nicaddct.html|title=Division of Periodontology: Tobacco Use Cessation Program |publisher=.umn.edu |date= |accessdate=2012-12-19}}</ref> Like other physically addictive drugs,{{citation needed|date=November 2013}} [[nicotine withdrawal]] causes [[downregulation]] of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. As dopamine regulates the sensitivity of nicotinic [[acetylcholine]] receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, [[convoluting]] its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. An example is the increase in [[norepinephrine]], one of the successors to dopamine, which inhibit reuptake of the [[glutamate receptors]],<ref name="pmid6493048">{{cite journal | author = Yoshida T, Nishioka H, Nakamura Y, Kondo M | title = Reduced norepinephrine turnover in mice with monosodium glutamate-induced obesity | journal = Metab. Clin. Exp. |volume = 33 | issue = 11 | pages = 1060–3 |date=November 1984 | pmid = 6493048 | doi = 10.1016/0026-0495(84)90238-5 }}</ref> in charge of memory and cognition. The net effect is an increase in reward pathway sensitivity, the opposite of other addictive drugs such as cocaine and heroin, which reduce reward pathway sensitivity.<ref name=Kenny/> This alteration in neuronal chemistry can persist for months following the last administration.

===Immunology prevention===
[[File:Nicotin 8338.JPG|thumb|A model of a nicotine molecule]]

Because of the severe addictions and the harmful effects of smoking, vaccination protocols have been developed. The principle operates under the premise that if an antibody is attached to a nicotine molecule, it will be prevented from diffusing through the [[capillaries]], thus making it less likely that it ever affects the brain by binding to [[nicotinic acetylcholine receptors]].

These include attaching the nicotine molecule as a [[hapten]] to a protein carrier such as [[keyhole limpet hemocyanin]] or a safe modified bacterial toxin to elicit an active immune response. Often it is added with [[bovine serum albumin]].

Additionally, because of concerns with the unique immune systems of individuals being liable to produce antibodies against endogenous hormones and over-the-counter drugs, [[monoclonal antibodies]] have been developed for short term passive immune protection. They have half-lives varying from hours to weeks. Their half-lives depend on their ability to resist degradation from [[pinocytosis]] by [[epithelial cells]].<ref name="pmid19592672">{{cite journal | author = Peterson EC, Owens SM | title = Designing immunotherapies to thwart drug abuse | journal = Mol. Interv. | volume = 9 | issue = 3 | pages = 119–24 |date=June 2009 | pmid = 19592672 | pmc = 2743871 | doi = 10.1124/mi.9.3.5 }}</ref>

==Toxicology==
{{See also|Nicotine poisoning}}
{| class="wikitable" style="float:right; margin:0 0 0 1em;"
|-
! style="background:#f90;"|[[NFPA 704]]
|-
| style="text-align:left;"|{{NFPA 704|Health = 4|Flammability = 1|Reactivity = 0|}}
|}

The {{LD50}} of nicotine is 50&nbsp;mg/kg for [[rat]]s and 3&nbsp;mg/kg for [[mouse|mice]]. 30–60&nbsp;mg (0.5–1.0&nbsp;mg/kg) can be a lethal dosage for adult humans.<ref name=inchem /><ref>{{cite journal |author=Okamoto M, Kita T, Okuda H, Tanaka T, Nakashima T |title=Effects of aging on acute toxicity of nicotine in rats |journal=Pharmacol Toxicol. |volume=75 |issue=1 |pages=1–6 |date=Jul 1994 |pmid=7971729|doi=10.1111/j.1600-0773.1994.tb00316.x}}</ref> However the widely used human LD<sub>50</sub> estimate of 0.5–1.0&nbsp;mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit causing fatal outcomes is 500–1000&nbsp;mg of ingested nicotine, corresponding to an
oral LD50 of 6.5–13&nbsp;mg/kg .<ref name=MayerNewLethalDose2013>{{cite journal | author = Mayer B | title = How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century | journal = Arch. Toxicol. | volume = | issue = | pages = |date=October 2013 | pmid = 24091634 | doi = 10.1007/s00204-013-1127-0 }}</ref> Nevertheless nicotine has a relatively high [[toxicity]] in comparison to many other alkaloids such as [[cocaine]], which has an LD<sub>50</sub>of 95.1&nbsp;mg/kg when administered to mice. It is unlikely that a person would overdose on nicotine through smoking alone, although overdose can occur through combined use of nicotine patches or nicotine gum and cigarettes at the same time.<ref name=overdose />{{verify credibility|date=December 2013}} Spilling a high concentration of nicotine onto the skin can cause intoxication or even death, since nicotine readily passes into the bloodstream following dermal contact.<ref>{{cite journal |author=Lockhart LP |title=Nicotine poisoning |journal=Br Med J |volume=1 |issue= 3762|pages=246–7 |year=1933|doi=10.1136/bmj.1.3762.246-c}}</ref>

Historically, nicotine has not been regarded as a [[carcinogen]].{{Citation needed|date=February 2014}} The [[International Agency for Research on Cancer|IARC]] has not evaluated nicotine in its standalone form or assigned it to an official carcinogen group. While no epidemiological evidence supports that nicotine alone acts as a carcinogen in the formation of human cancer, research over the last decade has identified nicotine's [[carcinogenic]] potential in animal models and cell culture.<ref>{{cite journal |author=Hecht SS |title=Tobacco smoke carcinogens and lung cancer |journal=J. Natl. Cancer Inst. |volume=91 |issue=14 |pages=1194–210 |date=July 1999 |pmid=10413421 |doi=10.1093/jnci/91.14.1194}}</ref><ref>{{cite journal |author=Wu WK, Cho CH |title=The pharmacological actions of nicotine on the gastrointestinal tract |journal=J. Pharmacol. Sci. |volume=94 |issue=4 |pages=348–58 |date=April 2004 |pmid=15107574 |doi=10.1254/jphs.94.348}}</ref> Nicotine has been noted to directly cause cancer through a number of different mechanisms such as the activation of [[MAP Kinases]].<ref>{{cite journal |author=Chowdhury P, Udupa KB|title=Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation |journal=World J. Gastroenterol. |volume=12 |issue=46|pages=7428–32 |date=December 2006 |pmid=17167829 |url=http://www.wjgnet.com/1007-9327/full/v12/i46/7428.htm}}</ref> Indirectly, nicotine increases [[Nicotinic acetylcholine receptor|cholinergic]] signalling (and [[adrenergic receptor|adrenergic]] signalling in the case of colon cancer<ref>{{cite journal |author=Wong HP, Yu L, Lam EK, Tai EK, Wu WK, Cho CH |title=Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation |journal=Toxicol. Sci. |volume=97 |issue=2 |pages=279–87 |date=June 2007 |pmid=17369603 |doi=10.1093/toxsci/kfm060}}</ref>), thereby impeding apoptosis ([[programmed cell death]]), promoting tumor growth, and activating [[growth factors]] and cellular [[mitogenic]] factors such as [[5-Lipoxygenase|5-LOX]], and [[Epidermal growth factor|EGF]]. Nicotine also promotes cancer growth by stimulating [[angiogenesis]] and [[neovascularization]].<ref>{{cite journal |author=Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M |title=Nicotine enhances neovascularization and promotes tumor growth |journal=Mol. Cells|volume=16 |issue=2 |pages=143–6 |date=October 2003 |pmid=14651253 }}</ref><ref>{{cite journal |author=Ye YN, Liu ES, Shin VY, Wu WK, Luo JC, Cho CH |title=Nicotine promoted colon cancer growth via epidermal growth factor receptor, c-Src, and 5-lipoxygenase-mediated signal pathway|journal=J. Pharmacol. Exp. Ther. |volume=308 |issue=1 |pages=66–72 |date=January 2004 |pmid=14569062 |doi=10.1124/jpet.103.058321}}</ref> In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), [[metastasis]] (nine-fold increase), and tumor recurrence (threefold increase).<ref name="plosone.org">{{cite journal |author=Davis R, Rizwani W, Banerjee S, ''et al.'' |title=Nicotine promotes tumor growth and metastasis in mouse models of lung cancer |journal=PLoS ONE |volume=4 |issue=10 |pages=e7524 |year=2009 |pmid=19841737 |pmc=2759510 |doi=10.1371/journal.pone.0007524 |editor1-last=Pao |editor1-first=William|bibcode = 2009PLoSO...4.7524D }}</ref> [[N-Nitrosonornicotine|''N''-Nitrosonornicotine]] (NNN), classified by the IARC as a Group 1 carcinogen, is produced endogenously from nitrite in saliva and nicotine.

The [[teratogenesis|teratogenic]] properties of nicotine have been investigated. According to a study of about 77,000 pregnant women in Denmark,{{citation needed|date=March 2013}} women who used [[nicotine gum]] and patches during the early stages of pregnancy were found to face an increased risk of having babies with birth defects. The study showed that women who used nicotine-replacement therapy in the first 12 weeks of pregnancy had a 60% greater risk of having babies with birth defects compared to women who were non-smokers.{{citation needed|date=December 2013}}

Tobacco use among pregnant women has also been correlated to increased frequency of ADHD. Children born to mothers who used tobacco were two and a half times more likely to be diagnosed with ADHD.<ref>{{cite journal |author=Rauch, Stephen and Lanphear, Bruce |title=Prevention of Disability in Children:Elevating the Role of Environment |journal= Future of Children |volume=22 |issue=1 |year=2012|url=http://www.futureofchildren.org/futureofchildren/publications/docs/22_01_09.pdf |doi=10.1353/foc.2012.0006 |pages=193–217 |pmid=22550691}}</ref> Froelich estimated that "exposure to higher levels of lead and prenatal tobacco each accounted for 500,000 additional cases of ADHD in U.S. children".<ref>{{cite journal |doi=10.1542/peds.2009-0738 |title=Association of Tobacco and Lead Exposures with Attention-Deficit/Hyperactivity Disorder |year=2009 |last1=Froehlich |first1=T. E. |last2=Lanphear |first2=B. P. |last3=Auinger |first3=P. |last4=Hornung |first4=R. |last5=Epstein |first5=J. N. |last6=Braun |first6=J. |last7=Kahn |first7=R. S. |journal=Pediatrics |volume=124 |issue=6 |pages=e1054–63 |pmid=19933729 |pmc=2853804}}</ref>

Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the [[California Environmental Protection Agency]] added nicotine to the list of chemicals known to cause developmental toxicity.<ref>http://oehha.ca.gov/prop65/prop65_list/files/P65single121809.pdf{{full|date=December 2013}}</ref>

==Chemistry==
Nicotine is a [[hygroscopy|hygroscopic]], oily liquid that is [[miscible]] with [[water (molecule)|water]] in its [[base (chemistry)|base]] form. As a [[nitrogenous base]], nicotine forms [[salt]]s with [[acid]]s that are usually solid and water soluble. Its [[flash point]] is 95°C and its auto-ignition temperature is 244°C.<ref name=SLMSDS>[http://www.sciencelab.com/msds.php?msdsId=9926222 www.sciencelab.com/msds.php?msdsId=9926222] Material Safety Data Sheet
L-Nicotine MSDS</ref>

==Optical activity==
Nicotine is [[optically active]], having two [[enantiomer]]ic forms. The naturally occurring form of nicotine is [[levorotatory]] with a [[specific rotation]] of [α]<sub>D</sub> = –166.4° ((−)-nicotine). The [[dextrorotatory]] form, (+)-nicotine is physiologically less active than (–)-nicotine. (−)-nicotine is more toxic than (+)-nicotine.<ref>{{cite book|last=Gause|first=G. F.|title=Optical Activity and Living Matter|url=http://www.archive.org/stream/opticalactivityl00gauz/opticalactivityl00gauz_djvu.txt|editor=Luyet, B. J.|publisher=Biodynamica|location= Normandy, Missouri |year=1941|chapter=Chapter V: Analysis of various biological processes by the study of the differential action of optical isomers|volume=2|series= A series of monographs on general physiology}}</ref> The salts of (+)-nicotine are usually dextrorotatory.

==Biosynthesis==
[[File:Nicotine biosynthesis june 2012.png|thumb|300px|Nicotine biosynthesis]]
The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the [[pyridine]] ring of nicotine is derived from [[niacin]] (nicotinic acid) while the pyrrolidone is derived from N-methyl-Δ<sup>1</sup>-pyrrollidium cation.<ref>{{cite journal |doi=10.1016/0006-3002(59)90492-5 |title=Ornithine as a precursor for the pyrrolidine ring of nicotine |year=1959 |last1=Lamberts |first1=Burton L. |last2=Dewey |first2=Lovell J. |last3=Byerrum |first3=Richard U. |journal=Biochimica et Biophysica Acta |volume=33 |pages=22–6 |pmid=13651178 |issue=1}}</ref><ref>{{cite journal |doi=10.1021/ja01495a059 |title=The Biosynthesis of Nicotine from Isotopically Labeled Nicotinic Acids1 |year=1960 |last1=Dawson |first1=R. F. |last2=Christman |first2=D. R. |last3=d'Adamo |first3=A. |last4=Solt |first4=M. L. |last5=Wolf |first5=A. P. |journal=Journal of the American Chemical Society |volume=82 |issue=10 |pages=2628}}</ref> Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for niacin and the tropane pathway for N-methyl-Δ<sup>1</sup>-pyrrollidium cation.

The NAD pathway in the genus ''[[nicotiana]]'' begins with the oxidation of aspartic acid into α-imino succinate by aspartate oxidase (AO). This is followed by a condensation with [[glyceraldehyde-3-phosphate]] and a cyclization catalyzed by quinolinate synthase (QS) to give [[quinolinic acid]]. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form niacin mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of [[nicotinamide]] by the enzyme [[nicotinamidase]].{{citation needed|date=December 2013}}

The N-methyl-Δ<sup>1</sup>-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with [[decarboxylation]] of [[ornithine]] by ornithine decarboxylase (ODC) to produce [[putrescine]]. Putrescine is then converted into N-methyl putrescine via [[methylation]] by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes [[deamination]] into 4-methylaminobutanal by the N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-Δ<sup>1</sup>-pyrrollidium cation.{{citation needed|date=December 2013}}

The final step in the synthesis of nicotine is the coupling between N-methyl-Δ<sup>1</sup>-pyrrollidium cation and niacin. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of niacin into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-Δ<sup>1</sup>-pyrrollidium cation to form [[enantiomer]]ically pure (–)-nicotine.<ref name=plant-meta>{{cite book |editor1-first=Hiroshi |editor1-last=Ashihara |editor2-first=Alan |editor2-last=Crozier |editor3-first=Atsushi |editor3-last=Komamine |title=Plant metabolism and biotechnology |publisher=Wiley |location=Cambridge |isbn=978-0-470-74703-2}}{{page needed|date=December 2013}}</ref>

==Pharmacology==

===Pharmacokinetics===
As nicotine enters the body, it is distributed quickly through the [[blood]]stream and crosses the [[blood–brain barrier]] reaching the [[human brain|brain]] within 10–20 seconds after inhalation.<ref name="pmid12971663">{{cite journal | author = Le Houezec J | title = Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review | journal = Int. J. Tuberc. Lung Dis. | volume = 7 | issue = 9 | pages = 811–9 |date=September 2003 | pmid = 12971663 | doi = }}</ref> The [[elimination half-life]] of nicotine in the body is around two hours.<ref name="pmid7077531">{{cite journal | author = Benowitz NL, Jacob P, Jones RT, Rosenberg J | title = Interindividual variability in the metabolism and cardiovascular effects of nicotine in man | journal = J. Pharmacol. Exp. Ther. | volume = 221 | issue = 2 | pages = 368–72 |date=May 1982 | pmid = 7077531 | doi = }}</ref>

The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine,<ref>Russell MA, Jarvis M, Iyer R, Feyerabend C. Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J. 1980 April 5; 280(6219): 972–976.</ref> suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation".

Nicotine is [[metabolized]] in the [[liver]] by [[cytochrome P450]] enzymes (mostly [[CYP2A6]], and also by [[CYP2B6]]). A major metabolite is [[cotinine]]. Other primary metabolites include nicotine ''N'''-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.<ref name="pmid15734728">{{cite journal | author = Hukkanen J, Jacob P, Benowitz NL | title = Metabolism and disposition kinetics of nicotine | journal = Pharmacol. Rev. | volume = 57 | issue = 1 | pages = 79–115 |date=March 2005 | pmid = 15734728 | doi = 10.1124/pr.57.1.3 }}</ref> Under some conditions, other substances may be formed such as [[myosmine]].<ref>{{cite journal |title=The danger of third-hand smoke |journal=Chromatography Online |volume=7 |issue=3 |date=22 February 2011 |url=http://chromatographyonline.findanalytichem.com/lcgc/News/The-danger-of-third-hand-smoke/ArticleStandard/Article/detail/713385}}</ref>

[[Glucuronidation]] and oxidative metabolism of nicotine to cotinine are both inhibited by [[menthol]], an additive to [[menthol cigarettes|mentholated cigarettes]], thus increasing the half-life of nicotine ''in vivo''.<ref>{{cite journal |doi=10.1124/jpet.104.066902 |title=Mentholated Cigarette Smoking Inhibits Nicotine Metabolism |year=2004 |last1=Benowitz |first1=N. L. |journal=Journal of Pharmacology and Experimental Therapeutics |volume=310 |issue=3 |pages=1208–15 |pmid=15084646 |last2=Herrera |first2=B |last3=Jacob p |first3=3rd}}</ref>

===Detection of use===

====Medical detection====
Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a medicolegal death investigation. Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids.<ref>{{cite journal |author=Benowitz NL, Hukkanen J, Jacob P |title=Nicotine Psychopharmacology |pages=29–60 |year=2009 |pmid=19184645 |pmc=2953858 |doi=10.1007/978-3-540-69248-5_2 |series=Handbook of Experimental Pharmacology |isbn=978-3-540-69246-1 |volume=192 |chapter=Nicotine Chemistry, Metabolism, Kinetics and Biomarkers |issue=192 |journal=Handbook of experimental pharmacology }}</ref><ref>{{cite book |first=Randall Clint |last=Baselt |title=Disposition of Toxic Drugs and Chemicals in Man |year=2008 |publisher=Biomedical Publications |isbn=978-0-9626523-7-0 |edition=8th |pages=1103–7}}</ref> Nicotine use is not regulated in competitive sports programs.<ref>{{cite journal |author = Mündel, T. and Jones, D. A.|title = Effect of transdermal nicotine administration on exercise endurance in men|journal = Exp Physiol|year = 2006|volume = 91 |pmid = 16627574 |issue = 4| pages = 705–713 |doi = 10.1113/expphysiol.2006.033373 }}</ref>

===Pharmacodynamics===
Nicotine acts on the [[nicotinic acetylcholine receptor]]s, specifically the [[ganglion type nicotinic receptor]] and one [[Alpha-4 beta-2 nicotinic receptor|CNS nicotinic receptor]]. The former is present in the [[adrenal medulla]] and elsewhere, while the latter is present in the [[central nervous system]] (CNS). In small concentrations, nicotine increases the activity of these receptors. Nicotine also has effects on a variety of other neurotransmitters through less direct mechanisms.

====In the central nervous system====
[[File:NicotineDopaminergic WP1602.png|thumb|right|Effect of nicotine on dopaminergic neurons.]]
By binding to [[nicotinic acetylcholine receptor]]s, nicotine increases the levels of several [[neurotransmitter]]s&nbsp;– acting as a sort of "volume control". It is thought that increased levels of [[dopamine]] in the [[reward circuit]]s of the [[human brain|brain]] one of the major contributors of the apparent [[euphoria (emotion)|euphoria]] and [[relaxation (psychology)|relaxation]], and addiction caused by nicotine consumption. This release of dopamine induced by nicotine is thought to occur via a cholinergic–dopaminergic link, mediated by a neuropeptide, [[ghrelin]], in the [[ventral tegmentum]].<ref>{{cite journal |doi=10.1016/j.mce.2011.02.017 |title=The role of the central ghrelin system in reward from food and chemical drugs |year=2011 |last1=Dickson |first1=Suzanne L. |last2=Egecioglu |first2=Emil |last3=Landgren |first3=Sara |last4=Skibicka |first4=Karolina P. |last5=Engel |first5=Jörgen A. |last6=Jerlhag |first6=Elisabet |journal=Molecular and Cellular Endocrinology |volume=340 |pages=80–7 |pmid=21354264 |issue=1}}</ref> Nicotine has a higher affinity for [[acetylcholine]] receptors in the brain than those in [[skeletal muscle]], though at toxic doses it can induce contractions and respiratory paralysis.<ref>{{cite book |author=Katzung, Bertram G. |title=Basic and Clinical Pharmacology |publisher=McGraw-Hill Medical |location=New York |year=2006 |pages=99–105 }}</ref> Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.<ref name="pmid19252481">{{cite journal | author = Xiu X, Puskar NL, Shanata JA, Lester HA, Dougherty DA | title = Nicotine binding to brain receptors requires a strong cation-pi interaction | journal = Nature | volume = 458 | issue = 7237 | pages = 534–7 |date=March 2009 | pmid = 19252481 | pmc = 2755585 | doi = 10.1038/nature07768 |bibcode = 2009Natur.458..534X }}</ref>

Tobacco smoke contains [[anabasine]], [[anatabine]], and [[nornicotine]]. It also contains the [[monoamine oxidase inhibitor]]s [[Harmala alkaloid|harman]] and norharman.<ref name=pmid15582589>{{cite journal |author=Herraiz T, Chaparro C |title=Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors |journal=Biochem. Biophys. Res. Commun. |volume=326 |issue=2 |pages=378–86 |year=2005 |pmid=15582589 |doi=10.1016/j.bbrc.2004.11.033 }}</ref> These [[beta-carboline]] compounds significantly decrease [[MAO]] activity in smokers.<ref name="pmid15582589"/><ref name="pmid9549600">{{cite journal |author=Fowler JS, Volkow ND, Wang GJ, ''et al.'' |title=Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition |journal=J Addict Dis |volume=17 |issue=1 |pages=23–34 |year=1998 |pmid=9549600 |doi= 10.1300/J069v17n01_03 }}</ref> MAO [[enzyme]]s break down [[monoamine|monoaminergic neurotransmitters]] such as [[dopamine]], [[norepinephrine]], and [[serotonin]]. It is thought that the powerful interaction between the MAOIs and the nicotine is responsible for most of the addictive properties of tobacco smoking.<ref name="pmid14592678">{{cite journal |author=Villégier AS, Blanc G, Glowinski J, Tassin JP |title=Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors |journal=Pharmacol. Biochem. Behav. |volume=76 |issue=2 |pages=267–74 |date=September 2003 |pmid=14592678 |doi= 10.1016/S0091-3057(03)00223-5}}</ref> The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.<ref name="pmid16395299">{{cite journal | author = Villégier AS, Salomon L, Granon S, Changeux JP, Belluzzi JD, Leslie FM, Tassin JP | title = Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine | journal = Neuropsychopharmacology | volume = 31 | issue = 8 | pages = 1704–13 |date=August 2006 | pmid = 16395299 | doi = 10.1038/sj.npp.1300987 }}</ref>

Chronic nicotine exposure via tobacco smoking [[up-regulation|up-regulates]] [[alpha-4 beta-2 nicotinic receptor|alpha4beta2]]* nAChR in [[cerebellum]] and [[brainstem]] regions<ref name="pmid17997038">{{cite journal | author = Wüllner U, Gündisch D, Herzog H, Minnerop M, Joe A, Warnecke M, Jessen F, Schütz C, Reinhardt M, Eschner W, Klockgether T, Schmaljohann J | title = Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain | journal = Neurosci. Lett. | volume = 430 | issue = 1 | pages = 34–7 |date=January 2008 | pmid = 17997038 | doi = 10.1016/j.neulet.2007.10.011 }}</ref><ref name="pmid18174175">{{cite journal |author=Walsh H, Govind AP, Mastro R, ''et al.'' |title=Up-regulation of nicotinic receptors by nicotine varies with receptor subtype |journal=J. Biol. Chem. |volume=283 |issue=10 |pages=6022–32 |year=2008 |pmid=18174175 |doi=10.1074/jbc.M703432200 }}</ref> but not [[habenula|habenulopeduncular]] structures.<ref name="pmid14560040">{{cite journal |author=Nguyen HN, Rasmussen BA, Perry DC |title=Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography |journal=J. Pharmacol. Exp. Ther. |volume=307 |issue=3 |pages=1090–7 |year=2003 |pmid=14560040 |doi=10.1124/jpet.103.056408 }}</ref> Alpha4beta2 and alpha6beta2 receptors, present in the [[ventral tegmental area]], play a crucial role in mediating the reinforcement effects of nicotine.<ref name="pmid19020025">{{cite journal |author=Pons S, Fattore L, Cossu G, ''et al.'' |title=Crucial role of α4 and α6 nicotinic acetylcholine receptor subunits from ventral tegmental area in systemic nicotine self-administration |journal=J. Neurosci. |volume=28 |issue=47 |pages=12318–27 |date=November 2008 |pmid=19020025 |doi=10.1523/JNEUROSCI.3918-08.2008 |pmc=2819191}}</ref>

====In the sympathetic nervous system====
Nicotine also activates the [[sympathetic nervous system]],<ref>{{cite journal |author=Yoshida T, Sakane N, Umekawa T, Kondo M |title=Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress |journal=Physiol. Behav. |volume=55 |issue=1 |pages=53–7 |date=Jan 1994 |pmid=8140174 |doi=10.1016/0031-9384(94)90009-4}}</ref> acting via [[splanchnic nerves]] to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and noradrenaline) into the [[bloodstream]]. Nicotine also has an affinity for [[melanin]]-containing tissues due to its precursor function in melanin synthesis or due to the irreversible binding of melanin and nicotine. This has been suggested to underlie the increased [[nicotine dependence]] and lower [[smoking cessation]] rates in darker pigmented individuals. However, further research is warranted before a definite conclusive link can be inferred.<ref>{{cite journal |author=King G, Yerger VB, Whembolua GL, Bendel RB, Kittles R, Moolchan ET |title=Link between facultative melanin and tobacco use among African Americans |journal=Pharmacol. Biochem. Behav. |volume=92 |issue=4 |pages=589–96 |date=June 2009 |pmid=19268687 |doi=10.1016/j.pbb.2009.02.011}}</ref>

====In adrenal medulla====
[[File:NicotineChromaffinCells WP1603.png|thumb|300px|Effect of nicotine on chromaffin cells.]]
By binding to [[ganglion type nicotinic receptor]]s in the adrenal medulla nicotine increases flow of [[adrenaline]] (epinephrine), a stimulating [[hormone]] and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of [[calcium]] through voltage-gated calcium channels. Calcium triggers the [[exocytosis]] of [[Chromaffin cell|chromaffin granules]] and thus the release of [[epinephrine]] (and norepinephrine) into the [[bloodstream]]. The release of [[epinephrine]] (adrenaline) causes an increase in [[heart rate]], [[blood pressure]] and [[breathing|respiration]], as well as higher [[blood glucose]] levels.<ref name="Marieb" >{{cite book | author = Elaine N. Marieb and Katja Hoehn | title = Human Anatomy & Physiology (7th Ed.) | publisher = Pearson | pages = ? | year = 2007 | isbn = 0-8053-5909-5}}{{page needed|date=December 2013}}</ref>

Nicotine is the natural product of tobacco, having a half-life of 1 to 2 hours. [[Cotinine]] is an active metabolite of nicotine that remains in the blood for 18 to 20 hours, making it easier to analyze due to its longer half-life.<ref>{{cite journal |last=Bhalala |first=Oneil |title=Detection of Cotinine in Blood Plasma by HPLC MS/MS |journal=MIT Undergraduate Research Journal |volume=8 |date=Spring 2003 |pages=45–50 |url=http://www.docstoc.com/docs/89426297/Detection-of-Cotinine-in-Blood-Plasma-by-HPLC-MS-MS}}</ref>

==History and name==

===Name===
Nicotine is named after the tobacco plant ''[[Nicotiana tabacum]],'' which in turn is named after the [[France|French]] ambassador in [[Portugal]], [[Jean Nicot|Jean Nicot de Villemain]], who sent tobacco and seeds to [[Paris]] in 1560, and who promoted their medicinal use. The tobacco and its seeds were brought to Ambassador Nicot from [[Brazil]] by [[Luis de Gois]], a Portuguese colonist in [[São Paulo]].{{citation needed|date=December 2013}}

===Chemical identification===
Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of [[Germany]], who considered it a poison.<ref>{{cite journal |author=Posselt, W.; Reimann, L. |title=Chemische Untersuchung des Tabaks und Darstellung eines eigenthümlich wirksamen Prinzips dieser Pflanze |trans_title=Chemical investigation of tobacco and preparation of a characteristically active constituent of this plant|language=German |journal=Magazin für Pharmacie |volume=6 |issue=24 |pages=138–161 |year=1828 |url=http://books.google.com/books?id=cgkCAAAAYAAJ&pg=RA1-PA138}}</ref><ref name="pmid16463054">{{cite journal | author = Henningfield JE, Zeller M | title = Nicotine psychopharmacology research contributions to United States and global tobacco regulation: a look back and a look forward | journal = Psychopharmacology (Berl.) | volume = 184 | issue = 3–4 | pages = 286–91 |date=March 2006 | pmid = 16463054 | doi = 10.1007/s00213-006-0308-4 }}</ref> Its chemical [[empirical formula]] was described by [[Louis Melsens|Melsens]] in 1843,<ref>Melsens, Louis-Henri-Frédéric (1843) [http://books.google.com/books?id=j-E3AAAAMAAJ&pg=PA465#v=onepage&q&f=false "Note sur la nicotine,"] ''Annales de chimie et de physique'', third series, vol. 9, pages 465-479; see especially page 470. [Note: The empirical formula that Melsens provides is incorrect because at that time, chemists used the wrong atomic mass for carbon (6 instead of 12).]</ref> its structure was
discovered by [[Adolf Pinner]] and [[Richard Wolffenstein (chemist)|Richard Wolffenstein]] in 1893,<ref>{{cite journal |doi=10.1002/cber.189102401242 |title=Ueber Nicotin |year=1891 |last1=Pinner |first1=A. |last2=Wolffenstein |first2=R. |journal=Berichte der deutschen chemischen Gesellschaft |volume=24 |pages=1373}}</ref><ref>{{cite journal |doi=10.1002/cber.18930260165 |title=Ueber Nicotin. Die Constitution des Alkaloïds |year=1893 |last1=Pinner |first1=A. |journal=Berichte der deutschen chemischen Gesellschaft |volume=26 |pages=292}}</ref><ref>{{cite journal |doi=10.1002/ardp.18932310508 |title=Ueber Nicotin. I. Mitteilung |year=1893 |last1=Pinner |first1=A. |journal=Archiv der Pharmazie |volume=231 |issue=5–6 |pages=378}}</ref>{{Clarify|reason=It's not clear that Wolffenstein should be attributed credit for identifying the structure of nicotine. Please see the talk page.|date=March 2013}} and it was first synthesized by Amé Pictet and A. Rotschy in 1904.<ref>{{cite journal |doi=10.1002/cber.19040370206 |title=Synthese des Nicotins |year=1904 |last1=Pictet |first1=Amé |last2=Rotschy |first2=A. |journal=Berichte der deutschen chemischen Gesellschaft |volume=37 |issue=2 |pages=1225}}</ref>

===As an insecticide===
[[Tobacco]] was introduced to [[Europe]] in 1559, and by the late 17th century, it was used not only for [[smoking]] but also as an [[insecticide]]. After [[World War II]], over 2,500 tons of nicotine insecticide (waste from the tobacco industry) were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to [[mammal]]s.<ref name=Ujvary />

Currently, nicotine, even in the form of tobacco dust, is prohibited as a [[pesticide]] for [[organic farming]] in the United States.<ref>US Code of Federal Regulations. [http://www.law.cornell.edu/cfr/text/7/205.602 7 CFR 205.602 - Nonsynthetic substances prohibited for use in organic crop production]</ref><ref>Staff, IFOAM. [http://classic.ifoam.org/growing_organic/1_arguments_for_oa/criticisms_misconceptions/misconceptions_no7.html Criticisms and Frequent Misconceptions about Organic Agriculture: The Counter-Arguments: Misconception Number 7]</ref>{{dead link|date=February 2014}}

In 2008, the [[United States Environmental Protection Agency|EPA]] received a request, from the registrant, to cancel the registration of the last nicotine pesticide registered in the United States.<ref name=epacancel1>{{Cite journal | author = USEPA | title = Nicotine; Notice of Receipt of Request to Voluntarily Cancel a Pesticide Registration | journal = Federal Register | pages = 64320–64322 | date = 29 October 2008 | url = https://federalregister.gov/a/E8-25831| accessdate = 8 April 2012 }}</ref> This request was granted, and since 1 January 2014, this pesticide has not been available for sale.<ref name=epacancel2>{{Cite journal | author = USEPA | title = Nicotine; Product Cancellation Order | journal = Federal Register | pages = 26695–26696 | url =https://federalregister.gov/a/E9-12561 | date = 3 June 2009 | accessdate = 8 April 2012 }}</ref>

==See also==
*''[[Nicotiana rustica]]''
*''[[Nicotiana tabacum]]''
*[[Substance dependence]]
*[[Tobacco products]]

==References==
{{Reflist|35em}}

==Further reading==
{{refbegin|30em}}
*{{Cite journal |author=Bilkei-Gorzo A, Rácz I, Michel K, Darvas M, Rafael Maldonado López, Zimmer A.|title=A common genetic predisposition to stress sensitivity and stress-induced nicotine craving|journal=Biol. Psychiatry |year=2008 |volume=63 |pages= 164–71 |pmid=17570348 |doi=10.1016/j.biopsych.2007.02.010 |issue=2}}
*{{cite book
| editor1-last =Gorrod
| editor1-first =John W.
| editor2-last =Peyton
| editor2-first =Jacob,III
| title =Analytical Determination of Nicotine and Related Compounds and their Metabolites
| date =November 16, 1999
| publisher =Elsevier
| location =Amsterdam
| isbn =978-0-08-052551-8
}}
*{{Cite journal |author=Willoughby JO, Pope KJ, Eaton V |title=Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study |journal=Epilepsia |volume=44 |issue=9 |pages=1238–40 |date=Sep 2003 |pmid=12919397 |doi=10.1046/j.1528-1157.2003.11903.x}}
*{{Cite journal |author=Minna JD |title=Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer |journal=J Clin Invest. |volume=111 |issue=1 |pages=31–3 |date=Jan 2003 |pmid=12511585 |pmc=151841 |doi=10.1172/JCI17492 }}
*{{Cite journal |author=[[James Fallon|Fallon JH]], Keator DB, Mbogori J, Taylor D, Potkin SG |title=Gender: a major determinant of brain response to nicotine |journal=Int J Neuropsychopharmacol. |volume=8 |issue=1 |pages=17–26 |date=Mar 2005 |pmid=15579215 |doi=10.1017/S1461145704004730}}
*{{Cite journal |author=West KA, Brognard J, Clark AS, ''et al.'' |title=Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells |journal=J Clin Invest. |volume=111 |issue=1 |pages=81–90 |date=Jan 2003 |pmid=12511591 |pmc=151834 |doi=10.1172/JCI16147 }}
*[http://www.nida.nih.gov/researchreports/nicotine/nicotine.html National Institute on Drug Abuse]
*[http://www.erowid.org/plants/tobacco/tobacco.shtml Erowid information on tobacco]
{{refend}}

==External links==
{{commons category|Nicotine}}
*[http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=NCT Nicotine bound to proteins] in the [[Protein Data Bank|PDB]]
*[http://www.howstuffworks.com/nicotine.htm Description of nicotine mechanisms]
*[http://www.erowid.org/chemicals/nicotine/nicotine_data_sheet1.shtml Erowid Nicotine Vault : Nicotine Material Safety Data Sheet]
*{{cite journal |doi=10.1038/ncpgasthep0316 |title=Mechanisms of Disease: Nicotine—a review of its actions in the context of gastrointestinal disease |year=2005 |last1=Thomas |first1=Gareth AO |last2=Rhodes |first2=John |last3=Ingram |first3=John R |journal=Nature Clinical Practice Gastroenterology &#38; Hepatology |volume=2 |issue=11 |pages=536}}
*[http://www.cdc.gov/niosh/npg/npgd0446.html CDC - NIOSH Pocket Guide to Chemical Hazards]
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[[Category:Pyrrolidine alkaloids]]
[[Category:Neurotoxins]]
[[Category:Nicotinic agonists]]
[[Category:Plant toxin insecticides]]
[[Category:Pyridines]]
[[Category:Smoking]]
[[Category:Stimulants]]
[[Category:Pollinator decline pesticides]]
[[Category:Alkaloids found in Nicotiana]]
[[Category:Alkaloids found in Erythroxylum coca]]

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Revision as of 09:21, 5 March 2014

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