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Nicotine 1

Nicotine
Nicotine

Systematic (IUPAC) name

3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
Identifiers

CAS number [1]


54-11-5

ATC code [2] [3]


N07 BA01 QP53 AX13

PubChem [4]
CID 942

DrugBank [5]
DB00184

ChemSpider [6]
80863  

UNII [7]
6M3C89ZY6R  

Chemical data

Formula C H N
10 14 2
Mol. mass 162.26 g/mol

SMILES [8] [9]


eMolecules & PubChem

Physical data

Density 1.01 g/cm³

Melt. point -79 °C (-110 °F)

Boiling point 247 °C (477 °F)

Pharmacokinetic data

Bioavailability 20 to 45% (oral)

Metabolism hepatic

Half-life 2 hours

Therapeutic considerations

Pregnancy cat. D(US)


Nicotine 2

Legal status Unscheduled (AU) ? (UK) ? (US)

Dependence Medium to high


liability

Routes smoked (as smoking tobacco, mapacho, etc.), insufflated (as tobacco snuff or nicotine nasal spray), chewed (as
nicotine gum, tobacco gum or chewing tobacco), transdermal (as nicotine patch, nicogel or topical tobacco
paste), intrabuccal (as dipping tobacco, snuffs, dissolvable tobacco or creamy snuff), vaporized (as electronic
cigarette, etc.), directly inhaled (as nicotine inhaler), oral (as nicotini)
[10]
(what is this?)   (verify)

Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) that constitutes approximately
0.6–3.0% of the dry weight of tobacco,[11] [12] with biosynthesis taking place in the roots and accumulation
occurring in the leaves. It functions as an antiherbivore chemical with particular specificity to insects; therefore
nicotine was widely used as an insecticide in the past,[13] [14] and currently nicotine analogs such as imidacloprid
continue to be widely used. Nicotine is also found in several other members of the Solanaceae family, with small
amounts being present in species such as the Eggplant and Tomato.
In low concentrations (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant
in mammals and is the main factor responsible for the dependence-forming properties of tobacco smoking.
According to the American Heart Association, nicotine addiction has historically been one of the hardest addictions
to break, while the pharmacological and behavioral characteristics that determine tobacco addiction are similar to
those that determine addiction to drugs such as heroin and cocaine.[15] Nicotine content in cigarettes has slowly
increased over the years, and one study found that there was an average increase of 1.6% per year between the years
of 1998 and 2005. This was found for all major market categories of cigarettes.[16]

History and name


Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after Jean Nicot de Villemain,
French ambassador in Portugal, who sent tobacco and seeds from Brazil to Paris in 1560 and promoted their
medicinal use. Nicotine was first isolated from the tobacco plant in 1828 by German chemists Posselt & Reimann,
who considered it a poison.[17] Its chemical empirical formula was described by Melsens in 1843,[18] its structure
was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and it was first synthesized by A. Pictet and
Crepieux in 1904.[19]

Chemistry
Nicotine is a hygroscopic, oily liquid that is miscible with water in its base form. As a nitrogenous base, nicotine
forms salts with acids that are usually solid and water soluble. Nicotine easily penetrates the skin. As shown by the
physical data, free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at
308 K (35 °C; 95 °F) in air despite a low vapor pressure. Because of this, most of the nicotine is burned when a
cigarette is smoked; however, enough is inhaled to cause pharmacological effects.
Nicotine 3

Optical activity
Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory,
with [α]D = –166.4°. The dextrorotatory form, (+)-nicotine, has only one-half the physiological activity of
(–)-nicotine. It is therefore weaker in the sense that a higher dose is required to attain the same effects.[20] The salts
of (+)-nicotine are usually dextrorotatory.

Pharmacology

Pharmacokinetics
As nicotine enters the body, it is distributed
quickly through the bloodstream and can cross
the blood-brain barrier. On average it takes about
seven seconds for the substance to reach the
brain when inhaled. The half life of nicotine in
the body is around two hours.[22]

The amount of nicotine absorbed by the body


from smoking depends on many factors,
including the type of tobacco, whether the smoke
is inhaled, and whether a filter is used. For
chewing tobacco, dipping tobacco, snus and
snuff, which are held in the mouth between the
lip and gum, or taken in the nose, the amount
released into the body tends to be much greater
than smoked tobacco. Nicotine is metabolized in
the liver by cytochrome P450 enzymes (mostly
[21]
CYP2A6, and also by CYP2B6). A major Side effects of nicotine.

metabolite is cotinine.

Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and
nicotine glucuronide.[23]
Glucuronidation and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to
mentholated cigarettes, thus increasing the half-life of nicotine in vivo.[24]

Detection of use
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.[25] [26] Interestingly, nicotine use is not regulated in
competitive sports programs, yet the drug has been shown to have a significant beneficial effect on athletic
performance.[27]
Nicotine 4

Pharmacodynamics
Nicotine acts on the nicotinic acetylcholine receptors, specifically the ganglion type nicotinic receptor and one 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 CNS

By binding to nicotinic acetylcholine receptors, nicotine increases the


levels of several neurotransmitters - acting as a sort of "volume
control". It is thought that increased levels of dopamine in the reward
circuits of the brain are responsible for the euphoria and relaxation and
eventual addiction caused by nicotine consumption. 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.[28] Nicotine's selectivity is thought to be due to a
particular amino acid difference on these receptor subtypes.[29]

Tobacco smoke contains the monoamine oxidase inhibitors harman,


norharman,[30] anabasine, anatabine, and nornicotine. These
Effect of nicotine on dopaminergic neurons
compounds significantly decrease MAO activity in smokers.[30] [31]
MAO enzymes break down monoaminergic neurotransmitters such as
dopamine, norepinephrine, and serotonin.
Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem
regions[32] [33] but not habenulopeduncular structures.[34] Alpha4beta2 and alpha6beta2 receptors, present in the
ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.[35]

In SNS
Nicotine also activates the sympathetic nervous system,[36] 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 norepinephrine) into the bloodstream.
Nicotine also has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or its
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.[37]

In adrenal medulla

By binding to ganglion type nicotinic receptors 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
granules and thus the release of epinephrine (and norepinephrine) into
the bloodstream. The release of epinephrine (adrenaline) causes an Effect of nicotine on chromaffin cells

increase in heart rate, blood pressure and respiration, as well as higher


blood glucose levels.[38]

Nicotine is the natural product of tobacco, having a half-life of 1 to 2 hours. In the other hand, cotinine is the
metabolite of nicotine which remains in the blood for 18 to 20 hours, making it a more stable compound, which
Nicotine 5

results more desirable and easier to analyze due to its longer half-life.[39]

Psychoactive effects
Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.[40] First
causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes
stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness.[41] Like any stimulant, it may
very rarely cause the often catastrophically uncomfortable neuropsychiatric effect of akathisia. By reducing the
appetite and raising the metabolism, some smokers may lose weight as a consequence.[42] [43]
Smokers often report that cigarettes help relieve feelings of stress. However, the stress levels of adult smokers are
slightly higher than those of nonsmokers, adolescent smokers report increasing levels of stress as they develop
regular patterns of smoking, and smoking cessation leads to reduced stress . Far from acting as an aid for mood
control, nicotine dependency seems to exacerbate stress. This is confirmed in the daily mood patterns described by
smokers, with normal moods during smoking and worsening moods between cigarettes. Thus, the apparent relaxant
effect of smoking only reflects the reversal of the tension and irritability that develop during nicotine depletion.
Dependent smokers need nicotine to remain feeling normal.[44]
When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and
immediately stimulates the release of many chemical messengers including acetylcholine, norepinephrine,
epinephrine, vasopressin, arginine, dopamine, autocrine agents, and beta-endorphin.[45] This release of
neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance
concentration[46] 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[47] and increases sensitivity in brain reward
systems.[48] Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.[49]
Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which
produce a low level of blood nicotine.[50] This stimulates 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, pain-killing effect. Nicotine is unique in comparison to most
drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use.
Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant
reinforcing properties.[51] However, only after coadministration with an MAOI, such as those found in tobacco,
nicotine produces significant behavioral sensitization, a measure of addiction potential. This is similar in effect to
amphetamine.[52]
Nicotine gum, usually in 2-mg or 4-mg doses, and nicotine patches are available, as well as smokeless tobacco and
electronic cigarettes which do not have all the other ingredients in smoked tobacco.
Nicotine 6

Dependence and withdrawal


Modern research shows that nicotine acts on the brain to produce a
number of effects. Specifically, its addictive nature has been found to
show that nicotine activates reward pathways—the circuitry within the
brain that regulates feelings of pleasure and euphoria.[55]
Dopamine is one of the key neurotransmitters actively involved in the
brain. Research shows that by increasing the levels of dopamine within
A 21 mg patch applied to the left arm. The
the reward circuits in the brain, nicotine acts as a chemical with intense
Cochrane Collaboration finds that NRT increases
addictive qualities. In many studies it has been shown to be more a quitter's chance of success by 50 to 70%.
[53]
addictive than cocaine and heroin. Like other physically addictive But in 1990, researchers found that 93% of users
[54]
drugs, nicotine withdrawal causes down-regulation of the production of returned to smoking within six months.

dopamine and other stimulatory neurotransmitters as the brain attempts


to compensate for artificial stimulation. As dopamine regulates the In addition, 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 reputake of the glutamate receptors,[56] in charge of memory and cognition. The net effect is an increase in
reward pathway sensitivity, opposite of other drugs of abuse such as cocaine and heroin, which reduce reward
pathway sensitivity.[48] This neuronal brain alteration persists for months after administration ceases. Nicotine also
has the potential to cause dependence in many animals other than humans, assuming they were to consume it.

A study found that nicotine exposure in adolescent mice retards the growth of the dopamine system, thus increasing
the risk of substance abuse during adolescence.[57]

Immunology prevention
Because of the severe addictions and the harmful effects of smoking, vaccination protocols have been developed.
The principle is 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 to a hapten 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.[58]

Toxicology
The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 40–60 mg (0.5-1.0 mg/kg) can be a lethal dosage for
adult humans.[59] [60] Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine,
which has an LD50 of 95.1 mg/kg when administered to mice. It is unlikely that a person would overdose on nicotine
through smoking alone, although intoxication can occur through the excessive use of nicotine patches, gum, nasal
sprays or oral inhalers intended as smoking cessation aids.[61] [62] 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.[63]
Nicotine 7

The carcinogenic properties of nicotine in standalone form, separate from tobacco smoke, have not been evaluated
by the IARC, and it has not been assigned to an official carcinogen group. The currently available literature indicates
that nicotine, on its own, does not promote the development of cancer in healthy tissue and has no mutagenic
properties. However, nicotine and the increased cholinergic activity it causes have been shown to impede apoptosis,
which is one of the methods by which the body destroys unwanted cells (programmed cell death). Since apoptosis
helps to remove mutated or damaged cells that may eventually become cancerous, the inhibitory actions of nicotine
may create a more favourable environment for cancer to develop, though this also remains to be proven.[64]
Though the teratogenic properties of nicotine may or may not yet have been adequately researched, women who use
nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth
defects, according to a study of around 77,000 pregnant women in Denmark. The study found that women who use
nicotine-replacement therapy in the first 12 weeks of pregnancy have a 60 percent greater risk of having babies with
birth defects, compared to women who are non-smokers, the Daily Mail reported. The findings were published in the
journal Obstetrics and Gynaecology.
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 the state to cause developmental
toxicity, for the purposes of Proposition 65.[65]

Link to circulatory disease


Nicotine has very powerful effects on arteries throughout the body. Nicotine is a stimulant, it raises blood pressure,
and is a vasoconstrictor, making it harder for the heart to pump through the constricted arteries. It causes the body to
release its stores of fat and cholesterol into the blood.[66]
It has been speculated that nicotine increases the risk of blood clots by increasing plasminogen activator inhibitor-1,
though this has not been proven. Plasma fibrinogen levels are elevated in smokers and are further elevated during
acute COPD exacerbation. Also Factor XIII, which stabilizes fibrin clots, is increased in smokers. But neither of
these two effects has been shown to be caused by nicotine [67] as of 2009.
Peripheral circulation in arteries going to the extremities is also highly susceptible to the vasoconstrictor effects of
nicotine and the increased risk of clots and clogging.

Therapeutic uses
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 apparently be of therapeutic value. These are often
referred to as "Smoker’s Paradoxes".[68] 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 and other ingredients found in tobacco.
For instance, recent studies suggest that smokers require less frequent repeated revascularization after percutaneous
coronary intervention (PCI).[68] 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.[69] [70] Smoking also appears to
interfere with development of Kaposi's sarcoma in patients with HIV,[71].[72]
Nicotine reduces the chance of Breast cancer among women carrying the very high risk BRCA gene,[73]
preeclampsia,[74] and atopic disorders such as allergic asthma.[75] A plausible mechanism of action in these cases
may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process,
as nicotine has vasoconstrictive effects.[76]
Nicotine 8

Tobacco smoke has been shown to contain compounds capable of inhibiting MAO. Monoamine oxidase 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.[77] Many such
papers regarding Alzheimer's disease[78] and Parkinson's Disease[79] have been published. Recent studies find no
beneficial link between smoking and Alzheimer's disease and in some cases, suggest it may actually result in an
earlier onset of the disease.[80] [81] [82] [83] However, nicotine has been shown to delay the onset of Parkinson's
disease in studies involving monkeys and humans.[84] [85] [86]
Recent 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.[87]
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 was recently argued
that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine.[88] [89]
More recent research has found that mildly dependent users got some benefit from nicotine, but not those who were
highly dependent.[90] All of these studies are based only on observation, and no interventional (randomized) studies
have been done. Research on nicotine as administered through a patch or gum is ongoing.
Nicotine appears to improve ADHD symptoms. Some studies are focusing on benefits of nicotine therapy in adults
with ADHD.[91]
Nicotine (in the form of chewing gum or a transdermal patch) is being explored as an experimental treatment for
OCD. Small studies show some success, even in otherwise treatment-refractory cases.[92] [93] [94]

Research as a potential basis for an antipsychotic agent


When the metabolites of nicotine were isolated and their effect on first the animal brain and then the human brain in
people with schizophrenia were studied, it was shown that the effects helped with cognitive and negative symptoms
of schizophrenia. Therefore, the nicotinergic agents, as antipsychotics which do not contain nicotine but act on the
same receptors in the brain are showing promise as adjunct antipsychotics in early stages of FDA studies on
schizophrenia. The prepulse inhibition (PPI) is a phenomenon in which a weak prepulse attenuates the response to a
subsequent startling stimulus. Therefore, PPI is believed to have face, construct, and predictive validity for the PPI
disruption in schizophrenia, and it is widely used as a model to study the neurobiology of this disorder and for
screening antipsychotics.[95] Additionally, studies have shown that there are genes predisposing people with
schizophrenia to nicotine use.[96]
Therefore with these factors taken together the heavy usage of cigarettes and other nicotine related products among
people with schizophrenia may be explained and novel antipsychotic agents developed that have these effects in a
manner that is not harmful and controlled and is a promising arena of research for schizophrenia.

See also
• Nicotiana
• Nicotiana rustica
• Mapacho
• Nicotiana tabacum
• Tobacco
• Tobacco products
• Nicotinic acid (Niacin)
• Drug addiction
Nicotine 9

• Tobacco cessation
• Chantix
• Zyban
• Nicogel
• Nicotini
• NicVAX
• Nicotine gum
• Nicotine patch
• Nicotine inhaler
• Nicotine nasal spray
• Snus
• Electronic Cigarette
• Psychoactive drug
• Drug Discovery and Development: Nicotinic Acetylcholine Receptor Agonists
• Nicotinic receptor

References
[1] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2009/ MB_cgi?term=54-11-5& rn=1
[2] http:/ / www. whocc. no/ atc_ddd_index/ ?code=N07BA01
[3] http:/ / www. whocc. no/ atcvet/ atcvet_index/ ?code=QP53AX13
[4] http:/ / pubchem. ncbi. nlm. nih. gov/ summary/ summary. cgi?cid=942
[5] http:/ / www. drugbank. ca/ cgi-bin/ show_drug. cgi?CARD=DB00184
[6] http:/ / www. chemspider. com/ Chemical-Structure. 80863
[7] http:/ / fdasis. nlm. nih. gov/ srs/ srsdirect. jsp?regno=6M3C89ZY6R
[8] http:/ / www. emolecules. com/ cgi-bin/ search?t=ex& q=n1cc%28ccc1%29%5BC%40H%5D2N%28C%29CCC2
[9] http:/ / pubchem. ncbi. nlm. nih. gov/ search/ ?smarts=n1cc%28ccc1%29%5BC%40H%5D2N%28C%29CCC2
[10] http:/ / en. wikipedia. org/ w/ index. php?& diff=cur& oldid=398693012
[11] "Determination of the Nicotine Content of Various Edible Nightshades (Solanaceae) and Their Products and Estimation of the Associated
Dietary Nicotine Intake" (http:/ / pubs. acs. org/ cgi-bin/ abstract. cgi/ jafcau/ 1999/ 47/ i08/ abs/ jf990089w. html). . Retrieved 2008-10-05.
[12] "Smoking and Tobacco Control Monograph No. 9" (http:/ / dccps. nci. nih. gov/ tcrb/ monographs/ 9/ m9_3. PDF) (PDF). .
[13] The Chemical Components of Tobacco and Tobacco Smoke (http:/ / books. google. com/ books?id=RiwSYFgZ2fEC& pg=PA933&
lpg=PA933& dq=nicotine+ widely+ used+ pesticide& source=bl& ots=KaYsWIJLC_& sig=ZnDL_ENqpngDiOWi5ksxaU12TOc& hl=en&
ei=7uw_SueFHJSuswPK_YG3AQ& sa=X& oi=book_result& ct=result& resnum=2)
[14] Some Pesticides Permitted in Organic Gardening (http:/ / www. coopext. colostate. edu/ 4DMG/ VegFruit/ organic. htm)
[15] "Nicotine Addiction" (http:/ / www. americanheart. org/ presenter. jhtml?identifier=4753), American Hearth Association.
[16] Connolly, G. N; Alpert, H. R; Wayne, G. F; Koh, H (2007). "Trends in nicotine yield in smoke and its relationship with design
characteristics among popular US cigarette brands, 1997-2005". Tobacco Control 16 (5): e5. doi:10.1136/tc.2006.019695. PMID 17897974.
[17] Henningfield, JE; Zeller, M (2006). ""Nicotine psychopharmacology", research contributions to United States and global tobacco regulation:
A look back and a look forward" (http:/ / www. springerlink. com/ content/ 75462q6mq88g4575/ fulltext. pdf). Psychopharmacology 184
(3-4): 286–291. doi:10.1007/s00213-006-0308-4. PMID 16463054. .
[18] Melsens (1844). "Über das Nicotin". Journal für Praktische Chemie 32 (1): 372–377. doi:10.1002/prac.18440320155.
[19] Comptes rendus, 1903, 137, p 860 (http:/ / medicolegal. tripod. com/ toxicchemicals. htm)
[20] Gause, G. F. (1941). Luyet, B. J.. ed. (http:/ / www. archive. org/ stream/ opticalactivityl00gauz/ opticalactivityl00gauz_djvu. txt). No. 2 of a
series of monographs on general physiology. Normandy, Missouri: Biodynamica. .
[21] References and comments are found in image description in Commons.
[22] Benowitz NL, Jacob P 3rd, Jones RT, Rosenberg J, NL; Jacob P, 3rd; Jones, RT; Rosenberg, J (1982). "Interindividual variability in the
metabolism and cardiovascular effects of nicotine in man". J Pharmacol Exp Ther 221 (2): 368–72. PMID 7077531.
[23] Hukkanen J, Jacob P 3rd, Benowitz NL., J; Jacob P, 3rd; Benowitz, NL (March 2005). "Metabolism and Disposition Kinetics of Nicotine"
(http:/ / pharmrev. aspetjournals. org/ cgi/ content/ full/ 57/ 1/ 79). Pharmacol Rev. 57 (1): 79–115. doi:10.1124/pr.57.1.3. PMID 15734728. .
[24] Benowitz NL, Herrera B, Jacob P 3rd., NL; Herrera, B; Jacob P, 3rd (2004). "Mentholated Cigarette Smoking Inhibits Nicotine Metabolism"
(http:/ / jpet. aspetjournals. org/ cgi/ content/ abstract/ 310/ 3/ 1208). J Pharmacol Exp Ther 310 (3): 1208–15. doi:10.1124/jpet.104.066902.
PMID 15084646. .
[25] Benowitz NL, Hukkanen J, Jacob P. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb. Exp. Pharmacol. 192: 29-60, 2009.
[26] R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1103-1107.
Nicotine 10

[27] Mündel, T. and Jones, D. A. (2006). "Effect of transdermal nicotine administration on exercise endurance in men.". Exp Physiol 91 (4):
705–713. doi:10.1113/expphysiol.2006.033373. PMID 16627574.
[28] Katzung, Bertram G. Basic & Clinical Pharmacology (Basic and Clinical Pharmacology). New York: McGraw-Hill Medical, 2006. pages
99-105.
[29] Xinan Xiu, Nyssa L. Puskar, Jai A. P. Shanata, Henry A. Lester & Dennis A. Dougherty.(2009) "Nicotine binding to brain receptors requires
a strong cation– interaction". Nature 458:534-537 PMID 19252481
[30] Herraiz T, Chaparro C (2005). "Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and
reversible inhibitors". Biochem. Biophys. Res. Commun. 326 (2): 378–86. doi:10.1016/j.bbrc.2004.11.033. PMID 15582589.
[31] Fowler JS, Volkow ND, Wang GJ, et al. (1998). "Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B)
inhibition". J Addict Dis 17 (1): 23–34. doi:10.1300/J069v17n01_03. PMID 9549600.
[32] Wüllner U, Gündisch D, Herzog H, et al. (2008). "Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain".
Neurosci. Lett. 430 (1): 34–7. doi:10.1016/j.neulet.2007.10.011. PMID 17997038.
[33] Walsh H, Govind AP, Mastro R, et al. (2008). "Up-regulation of nicotinic receptors by nicotine varies with receptor subtype". J. Biol. Chem.
283 (10): 6022–32. doi:10.1074/jbc.M703432200. PMID 18174175.
[34] Nguyen HN, Rasmussen BA, Perry DC (2003). "Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in
rat brain demonstrated by receptor autoradiography". J. Pharmacol. Exp. Ther. 307 (3): 1090–7. doi:10.1124/jpet.103.056408.
PMID 14560040.
[35] Pons S, Fattore L, Cossu G, et al. (November 2008). "Crucial role of alpha4 and alpha6 nicotinic acetylcholine receptor subunits from
ventral tegmental area in systemic nicotine self-administration" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez&
artid=2819191). J. Neurosci. 28 (47): 12318–27. doi:10.1523/JNEUROSCI.3918-08.2008. PMID 19020025. PMC 2819191.
[36] Yoshida T, Sakane N, Umekawa T, Kondo M (Jan 1994). "Effect of nicotine on sympathetic nervous system activity of mice subjected to
immobilization stress" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ 0031-9384(94)90009-4). Physiol Behav. 55 (1): 53–7.
doi:10.1016/0031-9384(94)90009-4. PMID 8140174. .
[37] King G, Yerger VB, Whembolua GL, Bendel RB, Kittles R, Moolchan ET. Link between facultative melanin and tobacco use among
African Americans.(2009). Pharmacol Biochem Behav. 92(4):589-96. doi:10.1016/j.pbb.2009.02.011 PMID 19268687
[38] Elaine N. Marieb and Katja Hoehn (2007). Human Anatomy & Physiology (7th Ed.). Pearson. pp. ?. ISBN 0-805-35909-5.
[39] Detection of Cotinine in Blood Plasma by HPLC MS/MS (http:/ / web. mit. edu/ murj/ www/ v08/ v08-Reports/ v08-r2. pdf), MIT
Undergraduate Research Journal, Volume 8, Spring 2003, Massachusetts Institute of Technology
[40] Effective Clinical Tobacco Intervention (http:/ / www. ti. ubc. ca/ pages/ letter21. htm), Therapeutics Letter, issue 21, September–October
1997, University of British Columbia
[41] Gilbert Lagrue, François Lebargy, Anne Cormier, "From nicotinic receptors to smoking dependence: therapeutic prospects" Alcoologie et
Addictologie Vol. : 23, N° : 2S, juin 2001, pages 39S - 42
[42] Jean-Claude Orsini, "Dependence on tobacco smoking and brain systems controlling glycemia and appetite" Alcoologie et Addictologie Vol.
: 23, N° : 2S, juin 2001, pages 28S - 36S
[43] Smokers lose their appetite : Media Releases : News : The University of Melbourne (http:/ / uninews. unimelb. edu. au/ articleid_1898. html)
[44] Does cigarette smoking cause stress?. Parrott, Andy C. American Psychologist, Vol 54(10), Oct 1999, 817-820. doi:
[10.1037/0003-066X.54.10.817]
This citation will be automatically completed in the next few minutes. You can jump the queue or expand by hand (http:/ / en. wikipedia. org/
wiki/ Template:cite_doi/ _. 5b10. 1037. 2f0003-066x. 54. 10. 817. 5d)
[45] Chemically Correct: Nicotine (http:/ / www. bodybuilding. com/ fun/ par16. htm), Andrew Novick
[46] Rusted, J; Graupner, O'Connell, Nicholls (1994-05-05). "Does nicotine improve cognitive function?" (http:/ / www. springerlink. com/
content/ 75034q53031260j8/ ?p=afde608485604678839ab0e950be77f9& pi=0). Psychopharmacology (Springer-Verlag) (115): 547–549. .
Retrieved 2008-11-15.
[47] http:/ / chronicle. uchicago. edu/ 020328/ nicotine. shtml
[48] Kenny PJ, Markou A (Jun 2006). "Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in
reward sensitivity" (http:/ / www. nature. com/ npp/ journal/ v31/ n6/ full/ 1300905a. html). Neuropsychopharmacology 31 (6): 1203–11.
doi:10.1038/sj.npp.1300905. PMID 16192981. .
[49] Erowid Nicotine Vault : Dosage (http:/ / www. erowid. org/ chemicals/ nicotine/ nicotine_dose. shtml)
[50] Einstein, Stanley (1989). Drug and Alcohol Use: Issues and Factors. Springer. pp. 101–118. ISBN 0306413787.
[51] Guillem K, Vouillac C, Azar MR, et al. (September 2005). "Monoamine oxidase inhibition dramatically increases the motivation to
self-administer nicotine in rats". J. Neurosci. 25 (38): 8593–600. doi:10.1523/JNEUROSCI.2139-05.2005. PMID 16177026.
[52] Villégier AS, Blanc G, Glowinski J, Tassin JP (September 2003). "Transient behavioral sensitization to nicotine becomes long-lasting with
monoamine oxidases inhibitors". Pharmacol. Biochem. Behav. 76 (2): 267–74. doi:10.1016/S0091-3057(03)00223-5. PMID 14592678.
[53] Stead LF, Perera R, Bullen C, Mant D, Lancaster T. (2008). "Nicotine replacement therapy for smoking cessation" (http:/ / www2. cochrane.
org/ reviews/ en/ ab000146. html). Cochrane Database of Systematic Reviews Art. No.: CD000146. doi:10.1002/14651858.CD000146.pub3. .
Retrieved May 22, 2010.
[54] Millstone, Ken (February 13, 2007). "Nixing the patch: Smokers quit cold turkey" (http:/ / jscms. jrn. columbia. edu/ cns/ 2007-02-13/
millstone-coldturkeyquitters. html). Columbia.edu News Service. . Retrieved May 23, 2010.
Nicotine 11

[55] NIDA - Research Report Series - Tobacco Addiction - Extent, Impact, Delivery, and Addictiveness (http:/ / www. nida. nih. gov/
researchreports/ nicotine/ nicotine2. html)
[56] http:/ / www. sciencedirect. com/ science?_ob=ArticleURL& _udi=B6WN4-4CCGGN1-9P& _user=10& _coverDate=11%2F30%2F1984&
_rdoc=1& _fmt=high& _orig=search& _origin=search& _sort=d& _docanchor=& view=c& _searchStrId=1520587233&
_rerunOrigin=scholar. google& _acct=C000050221& _version=1& _urlVersion=0& _userid=10&
md5=5e43884bdf1f204eb2356e02096708bc& searchtype=a
[57] Nolley EP, Kelley BM (2007). "Adolescent reward system perseveration due to nicotine: studies with methylphenidate". Neurotoxicol
Teratol 29 (1): 47–56. doi:10.1016/j.ntt.2006.09.026. PMID 17129706.
[58] Peterson, Eric C., and Michael Owens. "Designing Immunotherapies to thwart drug abuse." Molecular Interventions June 2009: 119-23.
Print.
[59] Okamoto M, Kita T, Okuda H, Tanaka T, Nakashima T (Jul 1994). "Effects of aging on acute toxicity of nicotine in rats". Pharmacol
Toxicol. 75 (1): 1–6. doi:10.1111/j.1600-0773.1994.tb00316.x. PMID 7971729.
[60] IPCS INCHEM (http:/ / www. inchem. org/ documents/ pims/ chemical/ nicotine. htm#PartTitle:7. TOXICOLOGY)
[61] http:/ / learn. genetics. utah. edu/ content/ addiction/ drugs/ overdose. html
[62] http:/ / www. drugtext. org/ library/ articles/ coffin. htm
[63] Lockhart LP (1933). "Nicotine poisoning". Br Med J 1: 246–7. doi:10.1136/bmj.1.3762.246-c.
[64] "Toxicology" (http:/ / www. ebasedtreatment. org/ drugs/ treatment/ nicotine/ toxicology). eBasedTreatment. . Retrieved 2008-10-05.
[65] http:/ / oehha. ca. gov/ prop65/ prop65_list/ files/ P65single121809. pdf
[66] http:/ / www. nature. com/ ijo/ journal/ v25/ n8/ full/ 0801654a. html
[67] http:/ / www. ncbi. nlm. nih. gov/ sites/ entrez
[68] Cohen, David J.; Michel Doucet, Donald E. Cutlip, Kalon K.L. Ho, Jeffrey J. Popma, Richard E. Kuntz (2001). "Impact of Smoking on
Clinical and Angiographic Restenosis After Percutaneous Coronary Intervention" (http:/ / www. data-yard. net/ 34/
circulation_2001_104_773. htm). Circulation 104 (7): 773. doi:10.1161/hc3201.094225. PMID 11502701. . Retrieved 2006-11-06.
[69] Longmore, M., Wilkinson, I., Torok, E. Oxford Handbook of Clinical Medicine (Fifth Edition) p. 232
[70] Green JT, Richardson C, Marshall RW, et al. (Nov 2000). "Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis" (http:/
/ www3. interscience. wiley. com/ resolve/ openurl?genre=article& sid=nlm:pubmed& issn=0269-2813& date=2000& volume=14&
issue=11& spage=1429). Aliment Pharmacol Ther. 14 (11): 1429–34. doi:10.1046/j.1365-2036.2000.00847.x. PMID 11069313. .
[71] http:/ / jnci. oxfordjournals. org/ content/ 94/ 22/ 1712. full
[72] {{cite JNCI J Natl Cancer Inst (2002) 94 (22): 1712-1718. "Smoking Cuts Risk of Rare Cancer" (http:/ / www. data-yard. net/ 10b/ kaposi.
htm). UPI. March 29, 2001. . Retrieved 2006-11-06.
[73] Recer, Paul (May 19, 1998). "Cigarettes May Have an Up Side" (http:/ / www. forces. org/ evidence/ files/ brea. htm). Associated Press. .
Retrieved 2006-11-06.
[74] Lain, Kristine Y.; Robert W. Powers, Marijane A. Krohn, Roberta B. Ness, William R. Crombleholme, James M. Roberts (Nov 1991).
"Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure" (http:/ / www. data-yard. net/ 2/ 13/ ajog.
htm). American Journal of Obstetrics and Gynecology 181 (5): 908–14. PMID 11422156. . Retrieved 2006-11-06.
[75] Hjern, A; Hedberg A, Haglund B, Rosen M (June 2001). "Does tobacco smoke prevent atopic disorders? A study of two generations of
Swedish residents" (http:/ / www. data-yard. net/ 30/ asthma. htm). Clin Exp Allergy 31 (6): 908–14. doi:10.1046/j.1365-2222.2001.01096.x.
PMID 11422156. . Retrieved 2006-11-06.
[76] Lisa Melton (June 2006). "Body Blazes" (http:/ / www. sciam. com/ article. cfm?chanID=sa006& colID=5&
articleID=00080902-A2CF-146C-9D1E83414B7F0000). Scientific American: 24. .
[77] Fratiglioni, L; Wang HX (Aug 2000). "Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies". Behav
Brain Res 113 (1–2): 117–20. doi:10.1016/S0166-4328(00)00206-0. PMID 10942038.
[78] Thompson, Carol. "Alzheimer's disease is associated with non-smoking" (http:/ / www. forces. org/ evidence/ carol/ carol16. htm). .
Retrieved 2006-11-06.
[79] Thompson, Carol. "Parkinson's disease is associated with non-smoking" (http:/ / www. forces. org/ evidence/ carol/ carol36. htm). .
Retrieved 2006-11-06.
[80] "Alzheimer's Starts Earlier for Heavy Drinkers, Smokers" (http:/ / www. reuters. com/ article/ pressRelease/ idUS198346+ 17-Apr-2008+
PRN20080417). Reuters. 2008-04-17. . Retrieved 2008-06-27.
[81] Peck, Peggy (2002-07-25). "Smoking Significantly Increases Risk of Alzheimer's Disease Among Those Who Have No Genetic
Predisposition" (http:/ / www. docguide. com/ news/ content. nsf/ news/ 8525697700573E1885256C010043BDDC?OpenDocument&
c=Smoking Related Disorders& count=10& id=48dde4a73e09a969852568880078c249). . Retrieved 2008-06-27.
[82] Aggarwal NT, Bienias JL, Bennett DA, et al. (2006). "The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban
community population". Neuroepidemiology 26 (3): 140–6. doi:10.1159/000091654. PMID 16493200.
[83] Lerche Davis,, Jeanie (2004-03-22). "Smoking Speeds Dementia, Alzheimer's Disease" (http:/ / www. webmd. com/ smoking-cessation/
news/ 20040322/ smoking-speeds-dementia-alzheimers-disease). . Retrieved 2008-06-27.
[84] DeNoon, Daniel (2006-08-11). "Nicotine Slows Parkinson's Disease" (http:/ / www. webmd. com/ parkinsons-disease/ news/ 20060811/
nicotine-slows-parkinsons-disease). . Retrieved 2009-12-27.
[85] Peck, Peggy (2002-07-25). "Smoking Significantly Increases Risk of Alzheimer's Disease Among Those Who Have No Genetic
Predisposition" (http:/ / www. nutraingredients. com/ Research/ More-vitamin-B6-linked-to-lower-Parkinson-s-risk). . Retrieved 2009-12-27.
Nicotine 12

[86] Fox, Maggie (2007-10-24). "Nicotine may ease Parkinson's symptoms: U.S. study" (http:/ / www. reuters. com/ article/
idUSN2431402020071024). Reuters. . Retrieved 2009-12-27.
[87] "Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study" (http:/ / www. cnsforum. com/ commenteditem/
3c5dccdc-27fb-4b80-9516-ab81e3e4ea6c/ default. aspx). .
[88] de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ (Jul 2002). "Schizophrenia and tobacco smoking: a replication study in another US
psychiatric hospital" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S092099640100192X). Schizophr Res. 56 (1-2): 55–65.
doi:10.1016/S0920-9964(01)00192-X. PMID 12084420. .
[89] de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM (Mar 1995). "Schizophrenia and smoking: an epidemiological
survey in a state hospital" (http:/ / ajp. psychiatryonline. org/ cgi/ pmidlookup?view=long& pmid=7864277). Am J Psychiatry 152 (3): 453–5.
PMID 7864277. .
[90] Aguilar MC, Gurpegui M, Diaz FJ, de Leon J (Mar 2005). "Nicotine dependence and symptoms in schizophrenia: naturalistic study of
complex interactions". Br J Psychiatry 186: 215–21. doi:10.1192/bjp.186.3.215. PMID 15738502.
[91] "Attention-Deficit Hyperactivity Disorder" (http:/ / adam. about. com/ reports/ 000030_1. htm). . Retrieved 21 September 2009.
[92] Pasquini M, Garavini A, Biondi M (January 2005). "Nicotine augmentation for refractory obsessive-compulsive disorder. A case report".
Prog. Neuropsychopharmacol. Biol. Psychiatry 29 (1): 157–9. doi:10.1016/j.pnpbp.2004.08.011. PMID 15610960.
[93] Lundberg S, Carlsson A, Norfeldt P, Carlsson ML (November 2004). "Nicotine treatment of obsessive-compulsive disorder". Prog.
Neuropsychopharmacol. Biol. Psychiatry 28 (7): 1195–9. doi:10.1016/j.pnpbp.2004.06.014. PMID 15610934.
[94] Tizabi Y, Louis VA, Taylor CT, Waxman D, Culver KE, Szechtman H (January 2002). "Effect of nicotine on quinpirole-induced checking
behavior in rats: implications for obsessive-compulsive disorder" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S0006322301012070). Biol.
Psychiatry 51 (2): 164–71. doi:10.1016/S0006-3223(01)01207-0. PMID 11822995. .
[95] Suemaru K, Kohnomi S, Umeda K, Araki H., K; Kohnomi, S; Umeda, K; Araki, H (2008). "Alpha7 nicotinic receptor agonists have
reported to reverse the PPI disruption" (in Japanese). Nihon Shinkei Seishin Yakurigaku Zasshi 28 (3): 121–6. PMID 18646597.
[96] De Luca V, Wong AH, Muller DJ, Wong GW, Tyndale RF, Kennedy JL.(2004). "Evidence of association between smoking and alpha7
nicotinic receptor subunit gene in schizophrenia patients" . Neuropsychopharmacology 29(8):1522-6. PMID 15100704

Further reading
• Bilkei-Gorzo A, Rácz I, Michel K, Darvas M, Rafael Maldonado López, Zimmer A. (2008). "A common genetic
predisposition to stress sensitivity and stress-induced nicotine craving". Biol. Psychiatry 63 (2): 164–71.
doi:10.1016/j.biopsych.2007.02.010. PMID 17570348.
• Willoughby JO, Pope KJ, Eaton V (Sep 2003). "Nicotine as an antiepileptic agent in ADNFLE: an N-of-one
study" (http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&
issn=0013-9580&date=2003&volume=44&issue=9&spage=1238). Epilepsia 44 (9): 1238–40.
doi:10.1046/j.1528-1157.2003.11903.x. PMID 12919397.
• Minna JD (Jan 2003). "Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression
in the pathogenesis of lung cancer" (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&
artid=151841). J Clin Invest. 111 (1): 31–3. doi:10.1172/JCI17492. PMID 12511585. PMC 151841.
• Fallon JH, Keator DB, Mbogori J, Taylor D, Potkin SG (Mar 2005). "Gender: a major determinant of brain
response to nicotine" (http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=282494).
Int J Neuropsychopharmacol. 8 (1): 17–26. doi:10.1017/S1461145704004730. PMID 15579215.
• West KA, Brognard J, Clark AS, et al. (Jan 2003). "Rapid Akt activation by nicotine and a tobacco carcinogen
modulates the phenotype of normal human airway epithelial cells" (http://www.pubmedcentral.nih.gov/
articlerender.fcgi?tool=pmcentrez&artid=151834). J Clin Invest. 111 (1): 81–90. doi:10.1172/JCI16147.
PMID 12511591. PMC 151834.
• National Institute on Drug Abuse (http://www.nida.nih.gov/researchreports/nicotine/nicotine.html)
• Erowid information on tobacco (http://www.erowid.org/plants/tobacco/tobacco.shtml)
Nicotine 13

External links
• Description of nicotine mechanisms (http://www.howstuffworks.com/nicotine.htm)
Article Sources and Contributors 14

Article Sources and Contributors


Nicotine  Source: http://en.wikipedia.org/w/index.php?oldid=400112890  Contributors: 100110100, 24champion, 7pof7, A5, AAA!, ALoopingIcon, AThing, Acdx, Adashiel, Afluent Rider,
Agnosticaphid, Alansohn, AlexRochon, AlexanderPico, AlexiusHoratius, All.ya.little.triksters, Alphax, Ambreenkazmi, Anastrophe, AndreNatas, Ansell, Antjben, Anypodetos, Apothecia,
Aramgutang, Arcadian, Archfalhwyl, Ariel., AriesPrincess, Atif.t2, AtomicCactus, Atorpey, Atteppo, Avnjay, AxelBoldt, Azazell0, BBird, BL, Badger Drink, Badhotra, BananaFiend, Barek,
Bassbonerocks, Bayhemp, Beao, Beefnut, Beetstra, Benjah-bmm27, BennyD, Biglovinb, Bill52270, Binary TSO, BlackAce48, Bmarett, Bmwild, Bobo192, Bogsat, Bongwarrior, BorisTM, Brec,
Brendan19, Brianga, BrienIsSexy4, Brockert, Brokenfixer, Bruce39, Bthomas001, Bwmcmaste, C6541, Cacycle, Caliga10, Calvin 1998, CambridgeBayWeather, Can't sleep, clown will eat me,
Capricorn42, Card, CardinalDan, Carl.bunderson, Carlosp123, Casforty, Causa sui, Cflm001, Chem-awb, ChemNerd, Chinasaur, Chocolateboy, Chuckysaul, Closedmouth, Cometstyles,
Confuzion, Corp1117, Correogsk, Countchoc, CovenantD, CrazyChemGuy, Crazycomputers, Crxssi, Crystallina, Curps, Curtmack, CyberSach, Cyrius, D, D0nj03, DMacks, DPham4, DVD R W,
Daevatgl, Dakinijones, Dancter, Daniel5127, Danielkueh, Dark-side-of-moon, Dascripter, DeadEyeArrow, Deany12345, Dekisugi, Delldot, Delta G, Deor, DerHexer, Dfrg.msc, Dirkbb,
Discospinster, Dlohcierekim, Dmarquard, DogcatcherDrew, Donarreiskoffer, Download, Dr.K., Dragice, Drphilharmonic, Drumlinedude, Duja, EagleFan, Eastlaw, EddEdmondson, Edgar181,
Eequor, EgonWillighagen, EhJJ, El3ctr0nika, ElBenevolente, Electrickoolaid, Elkman, Enviroboy, Epbr123, Eric-Wester, Erikthunder, Everyking, Everything Else Is Taken, Ewlyahoocom,
Extremophile, Eye.earth, Falcon8765, Falk Lieder, Fdskjs, Fdssdf, Fireaxe888, Fluidhomefront, Flyguy649, Footballfan190, Forever24ilove, Fragglet, Frahnie, Fremsley, FreplySpang, Fribbler,
Fuzzform, Fvasconcellos, Gabbe, Gale Jackson, Gamsarah, Geedubber, Gene Nygaard, Gentgeen, Georgevtucker, Gilliam, Gimboid13, Gobonobo, Gogo Dodo, GooberGobbler, Googie man,
GraemeL, Graham king 3, Graham87, Grayshi, GregorB, Gregshortall, Gsmgm, Gustavb, Gwernol, Gyrofrog, Gzuckier, Gökhan, HJ Mitchell, Hadal, HaeB, Happysailor, Harthacnut, Hazillow,
Hdt83, Heah, HexaChord, Hirohisat, Hopur52009, Howlandvh, Hqb, II MusLiM HyBRiD II, Ich, IconicMarlboro, Idontknow610, Iladvocate, Iluvmeandbookz, Im.a.lumberjack, Imersion,
Ineffable3000, Invalidreality, Iridescent, Irishguy, IronGargoyle, Isangaft220, Ixfd64, J.delanoy, J04n, JFreeman, Ja3en, Jack834834834, Jan eissfeldt, Jauhienij, Javsav, Jaxl, Jaysweet, Jeff G.,
Jfdwolff, Jfurr1981, Jh51681, Jijie, Jimmy joe joeseph, JinJian, Jlam4911, John, John Riemann Soong, JohnCD, JohnnyTwain, Jooyoonchung, Jpoelma13, Jrockley, Jsellick100, Jumbuck,
Jusdafax, JustAGal, Jusyc, Jv821, K10wnsta, Kansas Sam, Karl Stas, Karl-Henner, Kartano, Keilana, Kerowyn, Khukri, King of Hearts, Kipala, Knowledge Seeker, Korky Day, KorsteN, Kpjas,
Kpstewart, Krellis, Kristen1613, KristinaHanspers, Lakers, LarryGilbert, Lavidia, LeilaniLad, Lenoxus, Leptictidium, Leslieterada, Liamdaly620, Liftarn, Linkspamremover, Linnilou7,
LittleHow, LittleOldMe, Lofilt, Looie496, Loonymonkey, Luna Santin, MJ94, MPerel, Madhero88, Madman, Marbee, Maria mdv, Mark Zinthefer, Marqueed, MarsRover, Martial75, Martin
Kozák, Martinor, MattKingston, MauriceReeves, Mav, MaxEspinho, Maximus Rex, Mayooranathan, Mcsven, Mdpatrick, Meand, Medos2, Merope, Merqurial, Metalhead1994, Metalhead94,
MichaelJanich, Mikael Häggström, Mike19772007, Mikevick, Milamber au, Mindjuicer, Miniyazz, Mirgrim, Moira harrington, Mona, Mononomic, Montrealais, Mouse Nightshirt, Mouserunner,
Mr Bungle, Mr. Stabs, Mr0t1633, Mrmiscellanious, Mstroeck, Muchie11791, Muslim4eva, Muugokszhiion, Mvv1827, Myanw, NYKevin, Nandesuka, Necromankas, Negaluke, Neptunius, Nick
Michael, NickW557, Niubrad, Nucleophilic, Nutriveg, OAC, Oasisbob, Ohnoitsjamie, Okiefromokla (old), Olivier, Onorem, Owen, Ozzykhan, Paknightpa, Paleorthid, Palica, ParisianBlade,
Pascal666, Peabody80, Persephone12, PhilKnight, Philip Trueman, Philliesfan035, Phlegat, Physchim62, Pieter1, Pinkadelica, PinkcessAR, Pjc51, Plasticup, Pogue, Pol098, Pontificalibus, Popo
le Chien, Proquence, Protious, Pyrzqxgl, Quantpole, RDBrown, RG2, RJFJR, Raburton, Radon210, Ralph pr, Rave23, Razorflame, Rbaselt, Reillyd, Rich Farmbrough, Richard001, Rjwilmsi,
Rockjet, Rodhullandemu, RoyBoy, Rumping, SKEpptic, SWAdair, SYSS Mouse, Saadpralard, Sagaciousuk, Sameer94, Sapfan, ScAvenger, Sceptre, Schaefer, Scheinwerfermann,
Schmausschmaus, Septegram, Seven of Nine, Sfiller, Shaddack, Shiznick, Silentlight, Silly rabbit, SimonP, SkankBitch, Slakr, Slapazoid, Sliggy, Slyguy, Smalljim, SmartGuy, Smooth O,
SmthManly, Snowolf, Someguy1221, Soporaeternus, Spiritia, Stephenb, Stone, Sturm55, Sub40Hz, Suboptimal Username, Surly Dwarf, Susan Mason, SusanLesch, Sverdrup, TUF-KAT,
Tarquin, Techman224, Teles, Thaddeusjwhoopie, Thatguyflint, The Anome, The Rambling Man, The Right Honourable, The Thing That Should Not Be, The sock that should not be, The
undertow, Thehelpfulone, Thingg, Thoric, Thorne, TimVickers, TimeLord mbw, Tom X. Tobin, Tom harrison, TomasBat, Torria78, Travis.Thurston, Trimp, Trusilver, Tryptofish, Tsanth,
Tschwenn, TwinsMetsFan, UberMan5000, Ucanlookitup, Underwatercolor, Vanderesch, Vanished User 1004, Velvetron, Vicki Rosenzweig, Vidsp48, VigilancePrime, Vipinhari, Vivin,
Vrenator, Waninge, Wapcaplet, Wasell, Wavelength, Whiskey in the Jar, Willking1979, Willtron, Wimt, WojPob, Woodyblues, Woohookitty, Xcomradex, Yarnalgo, Yashgaroth, Yath, Yayay,
Yidisheryid, Yosri, Zefryl, Zenohockey, Zionicman, Zrenner, Zvi Zig, ‫طبلا يلع نسح‬, 1149 anonymous edits

Image Sources, Licenses and Contributors


file:Nicotine.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Nicotine.svg  License: Public Domain  Contributors: User:Harbin
file:Nicotine-3D-vdW.png  Source: http://en.wikipedia.org/w/index.php?title=File:Nicotine-3D-vdW.png  License: Public Domain  Contributors: Benjah-bmm27, Ies, Kemikungen
File:Yes check.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Yes_check.svg  License: Public Domain  Contributors: User:Gmaxwell, User:WarX
File:Side effects of nicotine.png  Source: http://en.wikipedia.org/w/index.php?title=File:Side_effects_of_nicotine.png  License: Public Domain  Contributors: Mikael Häggström
File:NicotineDopaminergic WP1602.png  Source: http://en.wikipedia.org/w/index.php?title=File:NicotineDopaminergic_WP1602.png  License: Creative Commons Attribution-Sharealike 3.0
 Contributors: Kristina Hanspers
File:NicotineChromaffinCells WP1603.png  Source: http://en.wikipedia.org/w/index.php?title=File:NicotineChromaffinCells_WP1603.png  License: Creative Commons Attribution-Sharealike
3.0  Contributors: Kristina Hanspers
Image:Nicoderm.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Nicoderm.JPG  License: Creative Commons Attribution 2.5  Contributors: BorgQueen, RegBarc, 2 anonymous
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