Nicotine
1
Nicotine
Nicotine
Systematic (IUPAC) name
3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
Clinical data
Trade names
AHFS/Drugs.com
Pregnancy cat.
Legal status
Nicorette, Nicotrol
[1]
monograph
D (US)
Unscheduled (AU) GSL (UK) OTC (US)
Dependence liability Very high
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), buccal (as snus)
Pharmacokinetic data
Bioavailability
Metabolism
Half-life
20 to 45% (oral)
hepatic
2 hours; 20 hours active metabolite (cotinine)
Identifiers
CAS number
54-11-5
[2]
ATC code
N07BA01
PubChem
CID 942
IUPHAR ligand
2585
[6]
[3]
[5]
QP53AX13
[4]
Nicotine
2
DrugBank
ChemSpider
UNII
[7]
DB00184
80863
[8]
6M3C89ZY6R
[10]
KEGG
D03365
ChEBI
CHEBI:18723
ChEMBL
[9]
CHEMBL3
[11]
[12]
Chemical data
Formula
Mol. mass
C10H14N2
162.12 g/mol
Physical data
Density
1.01 g/cm³
Melt. point
-79 °C (-110 °F)
Boiling point
247 °C (477 °F)
(what is this?) (verify)
[13]
Nicotine is a potent parasympathomimetic alkaloid found in the nightshade family of plants (Solanaceae). It acts as a
nicotinic acetylcholine receptor agonist. It 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[14] and is present in the range of 2–7 µg/kg of
various edible plants.[] It functions as an antiherbivore chemical; therefore, nicotine was widely used as an
insecticide in the past[15][16][] and nicotine analogs such as imidacloprid are currently widely used.
In smaller doses (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in
mammals, while high amounts (30–60 mg[]) can be fatal.[] This stimulant effect is likely a major contributing factor
to the dependence-forming properties of tobacco smoking.[citation needed] 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 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.[17]
Research in 2011 has found that nicotine inhibits chromatin-modifying enzymes (class I and II histone deacetylases)
which increases the ability of cocaine to cause an addiction.[18]
History and name
Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in
Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560, and who promoted their medicinal
use. The tobacco and seeds were brought to ambassador Nicot from Brazil by Luis de Gois, a Portuguese colonist in
São Paulo. 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.[19][] Its chemical empirical formula was
described by Melsens in 1843,[20] its structure was discovered by Adolf Pinner and Richard Wolffenstein in
1893,[21]Wikipedia:Please clarify and it was first synthesized by Amé Pictet and A. Rotschy in 1904.[22]
Nicotine
3
Historical use of nicotine 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 mammals.[16]
Currently, nicotine, even in the form of tobacco dust, is a prohibited pesticide for organic farming. Nicotine is
currently listed by the Organic Materials Review Institute as a prohibited substance:
Status: Prohibited
Class: Crop Pest, Weed, and Disease Control
Origin: Nonsynthetic
Description: NOP Rule: 205.602(i)[23]
Nicotine sulfate sold for use as a pesticide is labeled "DANGER," indicating that it is highly toxic.[] However, in
2008, the EPA received a request to cancel the registration of the last nicotine pesticide registered in the United
States.[] This request was granted, and after 1 January 2014, this pesticide will not be available for sale.[]
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, for example nicotine sulfate which, being a solid, is
easier to handle in its use as an insecticide. (For retail use it is sold as solution in water ready for spraying.)[] Its flash
point is 95°C and its auto-ignition temperature is 244°C.[24]
Optical activity
Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory
with a specific rotation of [α]D = –166.4° ((−)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less
active than (–)-nicotine. (−)-nicotine is more toxic than (+)-nicotine.[25] The salts of (+)-nicotine are usually
dextrorotatory.
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-Δ1-pyrrollidium
cation.[26][27] Biosynthesis of the two
component structures proceeds via two
independent syntheses, the NAD pathway
for niacin and the tropane pathway for
N-methyl-Δ1-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
Nicotine biosynthesis
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.
The N-methyl-Δ1-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-Δ1-pyrrollidium cation.
The final step in the synthesis of nicotine is the coupling between N-methyl-Δ1-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-Δ1-pyrrollidium cation to form enantiomerically pure (–)-nicotine.[]
4
Nicotine
5
Pharmacology
Pharmacokinetics
As nicotine enters the body, it is distributed
quickly through the bloodstream and crosses the
blood–brain barrier reaching the brain within
10–20 seconds after inhalation.[] The elimination
half-life of nicotine in the body is around two
hours.[]
The amount of nicotine absorbed by the body
from smoking depends on many factors,
including the types 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.Wikipedia:Please clarify
Nicotine is metabolized in the liver by
cytochrome P450 enzymes (mostly CYP2A6,
and also by CYP2B6). A major metabolite is
cotinine.
[28]
Side effects of nicotine.
Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and
nicotine glucuronide.[] Under some conditions, other substances may be formed such as myosmine.[29]
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.[30]
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.[31][32] Nicotine use is not regulated in competitive sports
programs, yet the drug has been shown to have a significant beneficial effect on athletic endurance in subjects who
have not used nicotine before.[33]
Nicotine
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 the central nervous system
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 apparent euphoria and
relaxation, and 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.[34] Nicotine's selectivity is thought to be due to a
particular amino acid difference on these receptor subtypes.[]
Tobacco smoke contains anabasine, anatabine, and nornicotine. It also
contains the monoamine oxidase inhibitors harman and norharman.[]
Effect of nicotine on dopaminergic neurons.
These beta-carboline compounds significantly decrease MAO activity
in smokers.[][] MAO enzymes break down 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.[] The
addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous
self-administration in rats.[]
Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem
regions[][] but not habenulopeduncular structures.[] Alpha4beta2 and alpha6beta2 receptors, present in the ventral
tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.[]
In the sympathetic nervous system
Nicotine also activates the sympathetic nervous system,[35] 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.[36]
6
Nicotine
7
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 increase in heart rate,
blood pressure and respiration, as well as
higher blood glucose levels.[]
Effect of nicotine on chromaffin cells.
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.[37]
Psychoactive effects
Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.[38] 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.[39] 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 lose weight as a consequence.[40][41]
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 such as acetylcholine, norepinephrine, epinephrine,
vasopressin, histamine, arginine, serotonin, dopamine, autocrine agents, and beta-endorphin.[42] This release of
neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance
concentration[] 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[43] and increases sensitivity in brain reward
systems.[] Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.[44]
Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which
produce a low level of blood nicotine.[45] 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.[] However, 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.[]
Nicotine
8
Nicotine gum, usually in 2-mg or 4-mg doses, and nicotine patches are
available, as well as smokeless tobacco, nicotine lozenges and
electronic cigarettes.
Side effects
Nicotine increases blood pressure and heart rate in humans.[] Nicotine
can also induce potentially atherogenic genes in human coronary artery
endothelial cells.[] Microvascular injury can result through its action on
nicotinic acetylcholine receptors (nAChRs).[]
A study on rats showed that nicotine exposure abolishes the beneficial
and protective effects of estrogen on the hippocampus,[] an
estrogen-sensitive region of the brain involved in memory formation
and retention.
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%. But
in 1990, researchers found that 93% of users
[46]
returned to smoking within six months.
Dependence and withdrawal
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") – the circuitry within the brain that regulates feelings of pleasure and euphoria.[47]
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 more addictive than cocaine and heroin.[48][49][50] Like other
physically addictive drugs, 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,[] 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.[] This alteration in neuronal chemistry can persist for months
following the last administration.
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.[]
Immunology prevention
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.
A model of a nicotine molecule
Nicotine
9
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.[]
Toxicology
NFPA 704
The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage
for adult humans.[][51] 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 overdose can occur through combined use of nicotine patches or nicotine gum and
cigarettes at the same time.[] 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.[52]
Historically, nicotine has not been regarded as a carcinogen and the 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.[53][54] Nicotine has been noted to directly cause
cancer through a number of different mechanisms such as the activation of MAP Kinases.[55] Indirectly, nicotine
increases cholinergic signalling (and adrenergic signalling in the case of colon cancer[56]), thereby impeding
apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic
factors such as 5-LOX, and EGF. Nicotine also promotes cancer growth by stimulating angiogenesis and
neovascularization.[57][58] 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).[]
The teratogenic properties of nicotine has been investigated. According to a study of ca. 77,000 pregnant women in
Denmark,[citation needed] 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.
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.[59] 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".[60]
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.[61]
Nicotine
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 be of therapeutic value. These are often referred to as
"Smoker’s Paradoxes".[] 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, studies suggest that smokers require less frequent repeated revascularization after percutaneous
coronary intervention (PCI).[] 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.[][] Smoking also appears to interfere
with development of Kaposi's sarcoma in patients with HIV.[][]
Nicotine reduces the chance of preeclampsia,[] and atopic disorders such as allergic asthma.[]Wikipedia:Disputed
statement 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.[]
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.[]
Many such papers regarding Alzheimer's disease[62] and Parkinson's Disease[63] have been published. While tobacco
smoking is associated with an increased risk of Alzheimer's disease,[] there is evidence that nicotine itself has the
potential to prevent and treat Alzheimer's disease.[] Nicotine has been shown to delay the onset of Parkinson's
disease in studies involving monkeys and humans.[64][65][66] 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.[67]
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.[68]
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-medicate with nicotine.[69][70] Other
research found that mildly dependent users got some benefit from nicotine, but not those who were highly
dependent.[71]
Research at Duke University Medical Center found that nicotine may improve the symptoms of depression.[72]
Nicotine appears to improve ADHD symptoms. Some studies have focused on benefits of nicotine therapy in adults
with ADHD.[73]
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.[]
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.[][][]
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
10
Nicotine
with benefit in ulcerative colitis but a detrimental effect in Crohn's disease.[74][75]
References
[1] http:/ / www. drugs. com/ monograph/ nicotine. html
[2] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2009/ MB_cgi?term=54-11-5& rn=1
[3] http:/ / www. whocc. no/ atc_ddd_index/ ?code=N07BA01
[4] http:/ / www. whocc. no/ atcvet/ atcvet_index/ ?code=QP53AX13
[5] http:/ / pubchem. ncbi. nlm. nih. gov/ summary/ summary. cgi?cid=942
[6] http:/ / www. iuphar-db. org/ DATABASE/ LigandDisplayForward?ligandId=2585
[7] http:/ / www. drugbank. ca/ drugs/ DB00184
[8] http:/ / www. chemspider. com/ Chemical-Structure. 80863
[9] http:/ / fdasis. nlm. nih. gov/ srs/ srsdirect. jsp?regno=6M3C89ZY6R
[10] http:/ / www. kegg. jp/ entry/ D03365
[11] https:/ / www. ebi. ac. uk/ chebi/ searchId. do?chebiId=CHEBI:18723
[12] https:/ / www. ebi. ac. uk/ chembldb/ index. php/ compound/ inspect/ CHEMBL3
[13] http:/ / en. wikipedia. org/ w/ index. php?title=Special:ComparePages& rev1=420440849& page2=Nicotine
[20] Melsens, Louis-Henri-Frédéric (1843) "Note sur la nicotine," (http:/ / books. google. com/ books?id=j-E3AAAAMAAJ&
pg=PA465#v=onepage& q& f=false) 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).]
[21] See:
•
A. Pinner and R. Wolffenstein (1891) "Ueber Nicotin," (http:/ / onlinelibrary. wiley. com/ doi/ 10. 1002/ cber. 189102401242/ abstract)
Berichte der deutschen chemischen Gesellschaft, vol. 24, no.1, pages 1373-1377.
• A. Pinner (1893) "Ueber Nicotin. Die Constitution des Alkaloïds," (http:/ / gallica. bnf. fr/ ark:/ 12148/ bpt6k907284/ f294. image.
langEN) Berichte der deutschen chemischen Gesellschaft, vol. 26, pages 292-305.
• A. Pinner (1893) "Ueber Nicotin. I. Mitteilung," (http:/ / books. google. com/ books?id=DgY4AAAAMAAJ& pg=PA378#v=onepage&
q& f=false) Archive für Pharmacie, vol. 231, pages 378-448.
[22] Amé Pictet and A. Rotschy (1904) "Synthese des Nicotins," (http:/ / books. google. com/ books?id=Vl8oAAAAYAAJ&
pg=PA1225#v=onepage& q& f=false) Berichte der Deutschen Chemischen Gesellschaft, vol. 37, pages 1225-1235.
[23] http:/ / www. omri. org/ simple-gml-search/ results?page=12
[24] www.sciencelab.com/msds.php?msdsId=9926222 (http:/ / www. sciencelab. com/ msds. php?msdsId=9926222) Material Safety Data Sheet
L-Nicotine MSDS
[28] References and comments are found in image description in Commons.
[38] Effective Clinical Tobacco Intervention (http:/ / www. ti. ubc. ca/ pages/ letter21. htm), Therapeutics Letter, issue 21, September–October
1997, University of British Columbia
[41] Smokers lose their appetite : Media Releases : News : The University of Melbourne (http:/ / uninews. unimelb. edu. au/ articleid_1898. html)
[42] Chemically Correct: Nicotine (http:/ / www. bodybuilding. com/ fun/ par16. htm), Andrew Novick
[61] http:/ / oehha. ca. gov/ prop65/ prop65_list/ files/ P65single121809. pdf
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 (http://dx.doi.org/10.1016/j.biopsych.2007.02.010). PMID 17570348
(http://www.ncbi.nlm.nih.gov/pubmed/17570348).
• Gorrod, John W.; Peyton, Jacob,III, eds. (November 16 1999). Analytical Determination of Nicotine and Related
Compounds and their Metabolites. Amsterdam: Elsevier. p. 772. ISBN 0444500952.
• 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 (http://dx.doi.org/10.1046/j.1528-1157.2003.11903.x). PMID 12919397 (http://www.ncbi.nlm.nih.gov/pubmed/12919397).
• Minna JD (Jan 2003). "Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression
in the pathogenesis of lung cancer" (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151841). J Clin Invest.
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Nicotine
•
•
•
•
111 (1): 31–3. doi: 10.1172/JCI17492 (http://dx.doi.org/10.1172/JCI17492). PMC 151841 (http://www.
ncbi.nlm.nih.gov/pmc/articles/PMC151841). PMID 12511585 (http://www.ncbi.nlm.nih.gov/pubmed/
12511585).
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 (http://dx.doi.org/10.1017/
S1461145704004730). PMID 15579215 (http://www.ncbi.nlm.nih.gov/pubmed/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.ncbi.nlm.nih.gov/pmc/
articles/PMC151834). J Clin Invest. 111 (1): 81–90. doi: 10.1172/JCI16147 (http://dx.doi.org/10.1172/
JCI16147). PMC 151834 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151834). PMID 12511591
(http://www.ncbi.nlm.nih.gov/pubmed/12511591).
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)
External links
• Nicotine bound to proteins (http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=NCT) in the PDB
• Description of nicotine mechanisms (http://www.howstuffworks.com/nicotine.htm)
• Erowid Nicotine Vault : Nicotine Material Safety Data Sheet (http://www.erowid.org/chemicals/nicotine/
nicotine_data_sheet1.shtml)
• Mechanisms of Disease: nicotine – a review of its actions in the context of gastrointestinal disease (http://www.
nature.com/nrgastro/journal/v2/n11/full/ncpgasthep0316.html)
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Article Sources and Contributors
Article Sources and Contributors
Nicotine Source: https://en.wikipedia.org/w/index.php?oldid=561825127 Contributors: 00AgentBond93, 100110100, 100percentrecord, 24champion, 7pof7, A2-25, A5, AAA!, ALoopingIcon,
AThing, Acdx, AdamGomaa, Adashiel, Aderylak, Afluent Rider, Agnosticaphid, Alansohn, AlexRochon, AlexanderPico, AlexiusHoratius, All.ya.little.triksters, AllenZh, Allens, Alphax,
Amack43, Ambreenkazmi, AnalogWeapon, Anastrophe, AndreNatas, Anna Frodesiak, Ansell, Anthony Appleyard, Anthonyhcole, Antjben, Anypodetos, Apothecia, Aramgutang, Arcadian,
Archfalhwyl, Ariel., AriesPrincess, Astrot70, Atif.t2, AtomicCactus, Atorpey, Atteppo, Avnjay, AxelBoldt, Azazell0, BBird, BL, Badger Drink, Badhotra, BananaFiend, Barek, Bassbonerocks,
Bayhemp, Beao, Beefnut, Beetstra, Bekus, Ben Ben, Benjah-bmm27, BennyD, Biglovinb, Bill52270, Binary TSO, BlackAce48, Bloomingdedalus, Bmarett, Bmwild, Bobo192, Boghog, Bogsat,
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Caliga10, Calvin 1998, CambridgeBayWeather, Can't sleep, clown will eat me, Capricorn42, Card, CardinalDan, Carl.bunderson, Carlosp123, CaroleHenson, CarsonsDad, Casforty, Catgut,
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Image Sources, Licenses and Contributors
file:Nicotine.svg Source: https://en.wikipedia.org/w/index.php?title=File:Nicotine.svg License: Public Domain Contributors: Harbin
file:Nicotine3Dan.gif Source: https://en.wikipedia.org/w/index.php?title=File:Nicotine3Dan.gif License: GNU Free Documentation License Contributors: Fuse809
File:Yes check.svg Source: https://en.wikipedia.org/w/index.php?title=File:Yes_check.svg License: Public Domain Contributors: Anomie
File:X mark.svg Source: https://en.wikipedia.org/w/index.php?title=File:X_mark.svg License: Public Domain Contributors: User:Gmaxwell
File:Nicotine biosynthesis june 2012.png Source: https://en.wikipedia.org/w/index.php?title=File:Nicotine_biosynthesis_june_2012.png License: Creative Commons Attribution 3.0
Contributors: Ljanuar
File:Side effects of nicotine.svg Source: https://en.wikipedia.org/w/index.php?title=File:Side_effects_of_nicotine.svg License: Public Domain Contributors: Mikael Häggström
File:NicotineDopaminergic WP1602.png Source: https://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: https://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: https://en.wikipedia.org/w/index.php?title=File:Nicoderm.JPG License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: BorgQueen,
RegBarc, 2 anonymous edits
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