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→Therapeutic uses: Replacing poor sources with a recent systematic review per WP:MEDRS. Article is on nicotine not tobacco, using recent review to discuss nicotine on it's own. Benefits in dementia for nicotine on its own.
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| url = http://www.data-yard.net/34/circulation_2001_104_773.htm
| doi = 10.1161/hc3201.094225
| doi = 10.1161/hc3201.094225
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| accessdate = 2006-11-06
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have been published. 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 |issue= |pages=36 |year=2008 |pmid=19105840 |pmc=2642819 |doi=10.1186/1471-2318-8-36 |url=}}</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 |volume= |issue=192 |pages=511–34 |year=2009 |pmid=19184661 |doi=10.1007/978-3-540-69248-5_18 |url=}}</ref>
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.<ref>
⚫
Nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans.<ref>
{{cite news
| title = Alzheimer's Starts Earlier for Heavy Drinkers, Smokers
| publisher= Reuters
| date = 2008-04-17
| url = http://www.reuters.com/article/pressRelease/idUS198346+17-Apr-2008+PRN20080417
| accessdate =2008-06-27}}
</ref><ref>
{{cite web
| last = Peck
| first = Peggy
| title = Smoking Significantly Increases Risk of Alzheimer's Disease Among Those Who Have No Genetic Predisposition
| date = 2002-07-25
| url = http://www.docguide.com/news/content.nsf/news/8525697700573E1885256C010043BDDC?OpenDocument&c=Smoking%20Related%20Disorders&count=10&id=48dde4a73e09a969852568880078c249
| accessdate = 2008-06-27}}
</ref><ref>
{{cite journal |author=Aggarwal NT, Bienias JL, Bennett DA, ''et al.'' |title=The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban community population |journal=Neuroepidemiology |volume=26 |issue=3 |pages=140–6 |year=2006 |pmid=16493200 |doi=10.1159/000091654 }}
</ref><ref>
{{cite web
| last = Lerche Davis,
| first =Jeanie
| authorlink =
| title = Smoking Speeds Dementia, Alzheimer's Disease
| date = 2004-03-22
| url = http://www.webmd.com/smoking-cessation/news/20040322/smoking-speeds-dementia-alzheimers-disease
| accessdate = 2008-06-27}}
</ref>
⚫
However, nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans.<ref>
{{cite web
{{cite web
| last = DeNoon
| last = DeNoon
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| accessdate = 2009-12-27
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| work=Reuters}}
| work=Reuters}}
</ref> However 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>J Neurochem. 2011 Sep 2. doi: 10.1111/j.1471-4159.2011.07466.x.</ref>
</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>J Neurochem. 2011 Sep 2. doi: 10.1111/j.1471-4159.2011.07466.x.</ref>


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.<ref>{{cite web |url=http://www.cnsforum.com/commenteditem/3c5dccdc-27fb-4b80-9516-ab81e3e4ea6c/default.aspx |title=Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study}}</ref>
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.<ref>{{cite web |url=http://www.cnsforum.com/commenteditem/3c5dccdc-27fb-4b80-9516-ab81e3e4ea6c/default.aspx |title=Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study}}</ref>

Revision as of 02:05, 12 March 2012

This article is about the chemical compound. For other uses, see Nicotine (disambiguation).
Nicotine
Clinical data
Trade namesNicorette, Nicotrol
AHFS/Drugs.comMonograph
Dependence
liability		Medium to high
Routes of
administration		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)
ATC code
Legal status
Legal status
  • AU: Unscheduled
  • UK: Unscheduled
  • US: WARNING[1]Unscheduled, but age restricted.
Pharmacokinetic data
Bioavailability20 to 45% (oral)
Metabolismhepatic
Elimination half-life2 hours
Identifiers
  • 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.177 Edit this at Wikidata
Chemical and physical data
FormulaC10H14N2
Molar mass162.26 g/mol g·mol−1
3D model (JSmol)
Density1.01 g/cm3
Melting point−79 °C (−110 °F)
Boiling point247 °C (477 °F)
  • n1cc(ccc1)[C@H]2N(C)CCC2
  • InChI=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 checkY
  • Key:SNICXCGAKADSCV-JTQLQIEISA-N checkY
 ☒NcheckY (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,[2][3] 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,[4][5] and currently nicotine analogs such as imidacloprid continue to be widely used.

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 determining addiction to heroin and cocaine. 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.[6]

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.[7]

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 physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison.[8][9] Its chemical empirical formula was described by Melsens in 1843,[10] its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and it was first synthesized by A. Pictet and Crepieux in 1904.[11]

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.

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.[12] The salts of (+)-nicotine are usually dextrorotatory.

Pharmacology

Pharmacokinetics

Side effects of nicotine.[13]

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.[14] The elimination half-life of nicotine in the body is around two hours.[15]

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.[clarification needed][citation needed] 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.[16] Under some conditions, other substances may be formed such as myosmine.[17]

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.[18]

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.[19][20] 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.[21]

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

Effect of nicotine on dopaminergic neurons

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.[22] Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.[23]

Tobacco smoke contains anabasine, anatabine, and nornicotine.[citation needed] It also contains the monoamine oxidase inhibitors harman and norharman.[24] These beta-carboline compounds significantly decrease MAO activity in smokers.[24][25] MAO enzymes break down monoaminergic neurotransmitters such as dopamine, norepinephrine, and serotonin. It is thought that the powerful interaction between the MAOI's and the nicotine is responsible for most of the addictive properties of tobacco smoking.[26] The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.[27]

Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem regions[28][29] but not habenulopeduncular structures.[30] Alpha4beta2 and alpha6beta2 receptors, present in the ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.[31]

In the sympathetic nervous system

Nicotine also activates the sympathetic nervous system,[32] 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 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.[33]

Effect of nicotine on chromaffin cells

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.[34]

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.[35]

Psychoactive effects

Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.[36] 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.[37] 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.[38][39]

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.[40] This release of neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance concentration[41] and memory due to the increase of acetylcholine.[citation needed] It also appears to enhance alertness due to the increases of acetylcholine and norepinephrine.[citation needed] Arousal is increased by the increase of norepinephrine.[citation needed] 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[42] and increases sensitivity in brain reward systems.[43] 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.[46] 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.[26]

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.

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%.[47] But in 1990, researchers found that 93% of users returned to smoking within six months.[48]

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") —the circuitry within the brain that regulates feelings of pleasure and euphoria.[49]

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.[50][51][52] Like other physically addictive drugs, nicotine withdrawal causes down-regulation 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,[53] 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.[43] This neuronal brain alteration can persist for months after administration ceases.

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.[54]

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.[55] [citation needed]

Toxicology

See also: Nicotine poisoning
NFPA 704
NFPA 704
safety square
NFPA 704 four-colored diamondHealth 4: Very short exposure could cause death or major residual injury. E.g. VX gasFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
4
1
0

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.[56][57] 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.[58] 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.[59]

Historically, nicotine has not been regarded as a carcinogen and the IARC has not evaluated nicotine in its standalone form and 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.[60] [61] Nicotine has been noted to directly cause cancer through a number of different mechanisms such as the activation of MAP Kinases.[62] Indirectly, nicotine increases cholinergic signalling (and adrenergic signalling in the case of colon cancer[63]), 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.[64][65] 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).[66]

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% greater risk of having babies with birth defects, compared to women who are non-smokers.[citation needed]

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.[67]

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,[1].[71]

Nicotine reduces the chance of breast cancer among women carrying the very high risk BRCA gene,[72] preeclampsia,[73] and atopic disorders such as allergic asthma.[74] 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.[75]

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.[76] Many such papers regarding Alzheimer's disease[77] and Parkinson's Disease[78] have been published. While tobacco smoking is associated with an increased risk of alzheimer's disease,[79] there is evidence that nicotine itself has the potential to prevent and treat alzheimer's disease.[80] Nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans.[81][82][83] 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.[84]

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.[85]

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.[86][87] More recent research has found that mildly dependent users got some benefit from nicotine, but not those who were highly dependent.[88] 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.[89]

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.[90][91][92]

The relationship between smoking and inflammatory bowel disease is now 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.[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[weasel words] 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

Mechanisms of Disease: nicotine—a review of its actions in the context of gastrointestinal disease

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Determination of the Nicotine Content of Various Edible Nightshades (Solanaceae) and Their Products and Estimation of the Associated Dietary Nicotine Intake". Retrieved 2008-10-05.
  3. ^ "Smoking and Tobacco Control Monograph No. 9" (PDF).
  4. ^ Rodgman, Alan; Perfetti, Thomas A. (2009). The chemical components of tobacco and tobacco smoke. Boca Raton, FL: CRC Press. ISBN 1420078836Template:Inconsistent citations{{cite book}}: CS1 maint: postscript (link)
  5. ^ Some Pesticides Permitted in Organic Gardening
  6. ^ 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. PMC 2598548. PMID 17897974.
  7. ^ sciencemag.org - Epigenetics of Nicotine: Another Nail in the Coughing
  8. ^ W. Posselt and L. Reimann (1828) "Chemische Untersuchung des Tabaks und Darstellung eines eigenthümlich wirksamen Prinzips dieser Pflanze" (Chemical investigation of tobacco and preparation of a characteristically active constituent of this plant), Geiger's Magazin für Pharmacie, volume 6, number 24, pages 138-161.
  9. ^ Henningfield, JE; Zeller, M (2006). ""Nicotine psychopharmacology", research contributions to United States and global tobacco regulation: A look back and a look forward" (PDF). Psychopharmacology. 184 (3–4): 286–291. doi:10.1007/s00213-006-0308-4. PMID 16463054. {{cite journal}}: More than one of |author1= and |last1= specified (help); More than one of |author2= and |last2= specified (help)
  10. ^ Melsens (1844). "Über das Nicotin". Journal für Praktische Chemie. 32 (1): 372–377. doi:10.1002/prac.18440320155.
  11. ^ Comptes rendus, 1903, 137, p 860
  12. ^ Gause, G. F. (1941). "Chapter V: Analysis of various biological processes by the study of the differential action of optical isomers". In Luyet, B. J. (ed.). Optical Activity and Living Matter. A series of monographs on general physiology. Vol. 2. Normandy, Missouri: Biodynamica.
  13. ^ References and comments are found in image description in Commons.
  14. ^ Le Houezec, J. (2003). "Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review". Int J Tuberc Lung Dis. 7 (9): 811–9. PMID 12971663. {{cite journal}}: Unknown parameter |month= ignored (help)
  15. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  16. ^ Hukkanen J, Jacob P 3rd, Benowitz NL., J; Jacob P, 3rd; Benowitz, NL (2005). "Metabolism and Disposition Kinetics of Nicotine". Pharmacol Rev. 57 (1): 79–115. doi:10.1124/pr.57.1.3. PMID 15734728. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  17. ^ http://chromatographyonline.findanalytichem.com/lcgc/News/The-danger-of-third-hand-smoke/ArticleStandard/Article/detail/713385
  18. ^ Benowitz NL, Herrera B, Jacob P 3rd., NL; Herrera, B; Jacob P, 3rd (2004). "Mentholated Cigarette Smoking Inhibits Nicotine Metabolism". J Pharmacol Exp Ther. 310 (3): 1208–15. doi:10.1124/jpet.104.066902. PMID 15084646.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  19. ^ Benowitz NL, Hukkanen J, Jacob P. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb. Exp. Pharmacol. 192: 29-60, 2009.
  20. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1103-1107.
  21. ^ 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. {{cite journal}}: Unknown parameter |unused_data= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Katzung, Bertram G. Basic & Clinical Pharmacology (Basic and Clinical Pharmacology). New York: McGraw-Hill Medical, 2006. pages 99-105.
  23. ^ Xiu, Xinan; Puskar, Nyssa L.; Shanata, Jai A. P.; Lester, Henry A.; Dougherty, Dennis A. (2009). "Nicotine Binding to Brain Receptors Requires a Strong Cation-π Interaction". Nature. 458 (7237): 534–537. doi:10.1038/nature07768. PMC 2755585. PMID 19252481.
  24. ^ a b 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.
  25. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  26. ^ a b Villégier AS, Blanc G, Glowinski J, Tassin JP (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Villégier, Anne-Sophie; Salomon, Lucas; Granon, Sylvie; Changeux, Jean-Pierre; Belluzzi, James D; Leslie, Frances M; Tassin, Jean-Pol (2006). "Monoamine Oxidase Inhibitors Allow Locomotor and Rewarding Responses to Nicotine". Nature. 31 (8): 1704. doi:10.1038/sj.npp.1300987.
  28. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  29. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  30. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Pons S, Fattore L, Cossu G; et al. (2008). "Crucial role of α4 and α6 nicotinic acetylcholine receptor subunits from ventral tegmental area in systemic nicotine self-administration". J. Neurosci. 28 (47): 12318–27. doi:10.1523/JNEUROSCI.3918-08.2008. PMC 2819191. PMID 19020025. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Yoshida T, Sakane N, Umekawa T, Kondo M (1994). "Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress". Physiol Behav. 55 (1): 53–7. doi:10.1016/0031-9384(94)90009-4. PMID 8140174. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ 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
  34. ^ Elaine N. Marieb and Katja Hoehn (2007). Human Anatomy & Physiology (7th Ed.). Pearson. pp. ?. ISBN 0-805-35909-5.
  35. ^ Detection of Cotinine in Blood Plasma by HPLC MS/MS, MIT Undergraduate Research Journal, Volume 8, Spring 2003, Massachusetts Institute of Technology
  36. ^ Effective Clinical Tobacco Intervention, Therapeutics Letter, issue 21, September–October 1997, University of British Columbia
  37. ^ 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
  38. ^ 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
  39. ^ Smokers lose their appetite : Media Releases : News : The University of Melbourne
  40. ^ Chemically Correct: Nicotine, Andrew Novick
  41. ^ Rusted, J (1994-05-05). "Does nicotine improve cognitive function?". Psychopharmacology (115). Springer-Verlag: 547–549. Retrieved 2008-11-15. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  42. ^ http://chronicle.uchicago.edu/020328/nicotine.shtml
  43. ^ a b Kenny PJ, Markou A (2006). "Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity". Neuropsychopharmacology. 31 (6): 1203–11. doi:10.1038/sj.npp.1300905. PMID 16192981. {{cite journal}}: Unknown parameter |month= ignored (help)
  44. ^ Erowid Nicotine Vault : Dosage
  45. ^ Einstein, Stanley (1989). Drug and Alcohol Use: Issues and Factors. Springer. pp. 101–118. ISBN 0306413787.
  46. ^ Guillem K, Vouillac C, Azar MR; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ Stead LF, Perera R, Bullen C, Mant D, Lancaster T. (2008). "Nicotine replacement therapy for smoking cessation". Cochrane Database of Systematic Reviews Art. No.: CD000146. doi:10.1002/14651858.CD000146.pub3. Retrieved May 22, 2010.{{cite web}}: CS1 maint: multiple names: authors list (link)
  48. ^ Millstone, Ken (February 13, 2007). "Nixing the patch: Smokers quit cold turkey". Columbia.edu News Service. Retrieved May 23, 2010.
  49. ^ NIDA - Research Report Series - Tobacco Addiction - Extent, Impact, Delivery, and Addictiveness
  50. ^ Hilts, Philip J. (1994-08-02). "Is Nicotine Addictive? It Depends on Whose Criteria You Use". The New York Times.
  51. ^ Blakeslee, Sandra (1987-03-29). "NICOTINE: HARDER TO KICK...THAN HEROIN". The New York Times.
  52. ^ http://www1.umn.edu/perio/tobacco/nicaddct.html
  53. ^ 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
  54. ^ 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.
  55. ^ Peterson, Eric C., and Michael Owens. "Designing Immunotherapies to thwart drug abuse." Molecular Interventions June 2009: 119-23. Print.
  56. ^ Okamoto M, Kita T, Okuda H, Tanaka T, Nakashima T (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ IPCS INCHEM
  58. ^ http://learn.genetics.utah.edu/content/addiction/drugs/overdose.html
  59. ^ Lockhart LP (1933). "Nicotine poisoning". Br Med J. 1 (3762): 246–7. doi:10.1136/bmj.1.3762.246-c.
  60. ^ Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 1999;91:1194-210.
  61. ^ Wu WK, Cho CH. The pharmacological actions of nicotine on the gastrointestinal tract. J Pharmacol Sci 2004;94:348-58.
  62. ^ Chowdhury P, Udupa KB. Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation. World J Gastroenterol 2006;12:7428-32.
  63. ^ Wong HP, Yu L, Lam EK, Tai EK, Wu WK, Cho CH. Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation. Toxicol Sci 2007;97:279-87.
  64. ^ Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M. Nicotine enhances neovascularization and promotes tumor growth. Mol Cells 2003;16:143-6.
  65. ^ Ye YN, Liu ES, Shin VY, Wu WK, Luo JC, Cho CH. Nicotine promoted colon cancer growth via epidermal growth factor receptor, c-Src, and 5-lipoxygenase-mediated signal pathway. J Pharmacol Exp Ther 2004;308:66-72.
  66. ^ http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007524
  67. ^ http://oehha.ca.gov/prop65/prop65_list/files/P65single121809.pdf
  68. ^ a b Cohen, David J. (2001). "Impact of Smoking on Clinical and Angiographic Restenosis After Percutaneous Coronary Intervention". Circulation. 104 (7): 773. doi:10.1161/hc3201.094225. PMID 11502701. Retrieved 2006-11-06. {{cite journal}}: More than one of |pages= and |page= specified (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  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. (2000). "Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis". Aliment Pharmacol Ther. 14 (11): 1429–34. doi:10.1046/j.1365-2036.2000.00847.x. PMID 11069313. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  71. ^ cite JNCI J Natl Cancer Inst (2002) 94 (22): 1712-1718. "Smoking Cuts Risk of Rare Cancer". UPI. March 29, 2001. Retrieved 2006-11-06.
  72. ^ Recer, Paul (May 19, 1998). "Cigarettes May Have an Up Side". Associated Press. Retrieved 2006-11-06.
  73. ^ Lain, Kristine Y. (1991). "Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure". American Journal of Obstetrics and Gynecology. 181 (5): 908–14. doi:10.1016/S0002-9378(99)70107-9. PMID 10561644. Retrieved 2006-11-06. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  74. ^ Hjern, A (2001). "Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents". Clin Exp Allergy. 31 (6): 908–14. doi:10.1046/j.1365-2222.2001.01096.x. PMID 11422156. Retrieved 2006-11-06. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  75. ^ Lisa Melton (2006). "Body Blazes". Scientific American: 24. {{cite journal}}: Unknown parameter |month= ignored (help)
  76. ^ Fratiglioni, L (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. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  77. ^ Thompson, Carol. "Alzheimer's disease is associated with non-smoking". Retrieved 2006-11-06.
  78. ^ Thompson, Carol. "Parkinson's disease is associated with non-smoking". Retrieved 2006-11-06.
  79. ^ Peters R, Poulter R, Warner J, Beckett N, Burch L, Bulpitt C (2008). "Smoking, dementia and cognitive decline in the elderly, a systematic review". BMC Geriatr. 8: 36. doi:10.1186/1471-2318-8-36. PMC 2642819. PMID 19105840.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  80. ^ Henningfield JE, Zeller M (2009). "Nicotine psychopharmacology: policy and regulatory". Handb Exp Pharmacol (192): 511–34. doi:10.1007/978-3-540-69248-5_18. PMID 19184661.
  81. ^ DeNoon, Daniel (2006-08-11). "Nicotine Slows Parkinson's Disease". Retrieved 2009-12-27.
  82. ^ Peck, Peggy (2002-07-25). "Smoking Significantly Increases Risk of Alzheimer's Disease Among Those Who Have No Genetic Predisposition". Retrieved 2009-12-27.
  83. ^ Fox, Maggie (2007-10-24). "Nicotine may ease Parkinson's symptoms: U.S. study". Reuters. Retrieved 2009-12-27.
  84. ^ J Neurochem. 2011 Sep 2. doi: 10.1111/j.1471-4159.2011.07466.x.
  85. ^ "Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study".
  86. ^ de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ (2002). "Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital". Schizophr Res. 56 (1–2): 55–65. doi:10.1016/S0920-9964(01)00192-X. PMID 12084420. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  87. ^ de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM (1995). "Schizophrenia and smoking: an epidemiological survey in a state hospital". Am J Psychiatry. 152 (3): 453–5. PMID 7864277. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  88. ^ Aguilar MC, Gurpegui M, Diaz FJ, de Leon J (2005). "Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions". Br J Psychiatry. 186 (3): 215–21. doi:10.1192/bjp.186.3.215. PMID 15738502. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  89. ^ "Attention-Deficit Hyperactivity Disorder". Retrieved 21 September 2009.
  90. ^ Pasquini M, Garavini A, Biondi M (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  91. ^ Lundberg S, Carlsson A, Norfeldt P, Carlsson ML (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  92. ^ Tizabi Y, Louis VA, Taylor CT, Waxman D, Culver KE, Szechtman H (2002). "Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder". Biol. Psychiatry. 51 (2): 164–71. doi:10.1016/S0006-3223(01)01207-0. PMID 11822995. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  93. ^ Thomas GA. Rhodes J. Green JT. Richardson C."Role of smoking in inflammatory bowel disease: implications for therapy. [Review] [72 refs]" Postgraduate Medical Journal. 76(895):273-9, 2000 May.
  94. ^ Rubin DT. Hanauer SB."Smoking and inflammatory bowel disease. [Review] [73 refs]" European Journal of Gastroenterology & Hepatology. 12(8):855-62, 2000 Aug.
  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". Nihon Shinkei Seishin Yakurigaku Zasshi (in Japanese). 28 (3): 121–6. PMID 18646597.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. doi:10.1038/sj.npp.1300466. PMID 15100704. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Unknown parameter |author-separator= ignored (help)

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