Mixing
Nicotine
 |
This article is in the process of an expansion or major restructuring. You are welcome to assist in its construction by editing it as well. This template was placed by User:Seppi333. If this article has not been edited in several days, please remove this template. If you are the editor who added this template and you are actively editing, please be sure to replace this template with {{in use}} during the active editing session. Click on the link for template parameters to use.This article was last edited by Greco22 (talk | contribs) 30 hours ago. (Update timer) |
 | |
 | |
| Clinical data | |
|---|---|
| Trade names | Nicorette, Nicotrol |
AHFS/Drugs.com |
Monograph |
| Pregnancy category |
|
| Dependence liability |
Physical: low–moderate Psychological: moderate–high[1][2] |
| Addiction liability |
High[3] |
| Routes of administration |
Inhalation; insufflation; oral – buccal, sublingual, and ingestion; transdermal; rectal |
| ATC code |
|
| Legal status | |
| Legal status |
|
Pharmacokinetic data | |
| Protein binding | <5% |
| Metabolism | Primarily hepatic: CYP2A6, CYP2B6, FMO3, others |
| Metabolites | Cotinine |
| Elimination half-life |
1-2 hours; 20 hours active metabolite |
| Excretion | Renal, urine pH-dependent;[5] 10–20% (gum), 30% (inhaled); 10–30% (intranasal) |
| Identifiers | |
IUPAC name
| |
| CAS Number |
|
PubChem CID |
|
| IUPHAR/BPS |
|
| DrugBank |
|
| ChemSpider |
|
| UNII |
|
| KEGG |
|
| ChEBI |
|
| ChEMBL |
|
PDB ligand |
|
| ECHA InfoCard | 100.000.177  |
| Chemical and physical data | |
| Formula | C10H14N2 |
| Molar mass | 162.23 g/mol g·mol−1 |
| 3D model (JSmol) |
|
| Chirality | Chiral |
| Density | 1.01 g/cm3 |
| Melting point | −79 °C (−110 °F) |
| Boiling point | 247 °C (477 °F) |
SMILES
| |
InChI
| |
Nicotine is a stimulant and potent parasympathomimetic alkaloid that is naturally produced in the nightshade family of plants and used for the treatment of tobacco use disorders as a smoking cessation aid and nicotine dependence for the relief of withdrawal symptoms.[4][6][7] Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs),[8][9][10] except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.[8]
Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco.[11] Usually consistent concentrations of nicotine varying from 2–7 µg/kg (20–70 millionths of a percent wet weight) are found in the edible family Solanaceae, such as potatoes, tomatoes, and eggplant.[12] Some research indicates that the contribution of nicotine obtained from food is substantial in comparison to inhalation of second-hand smoke.[12] Others consider nicotine obtained from food to be trivial unless exceedingly high amounts of certain vegetables are eaten.[12] It functions as an antiherbivore chemical; consequently, nicotine was widely used as an insecticide in the past,[13][14] and neonicotinoids, such as imidacloprid, are widely used.
Nicotine is highly addictive.[15][16][17] It is one of the most commonly abused drugs.[18] An average cigarette yields about 2 mg of absorbed nicotine; high amounts can be harmful.[19] Nicotine induces both behavioral stimulation and anxiety in animals.[5] Nicotine addiction involves drug-reinforced behavior, compulsive use, and relapse following abstinence.[20] Nicotine dependence involves tolerance, sensitization,[21]physical dependence, and psychological dependence.[22] Nicotine dependency causes distress.[23][24] Nicotine withdrawal symptoms include depressed mood, stress, anxiety, irritability, difficulty concentrating, and sleep disturbances.[1] Mild nicotine withdrawal symptoms are measurable in unrestricted smokers, who experience normal moods only as their blood nicotine levels peak, with each cigarette.[25] On quitting, withdrawal symptoms worsen sharply, then gradually improve to a normal state.[25]
Nicotine use as a tool for quitting smoking has a good safety history.[26] The general medical position is that nicotine itself poses few health risks, except among certain vulnerable groups,[27] such as youth.[28] The International Agency for Research on Cancer indicates that nicotine does not cause cancer.[29] Nicotine has been shown to produce birth defects in some animal species, but not others;[30] consequently, it is considered to be a possible teratogen in humans.[30] The median lethal dose of nicotine in humans is unknown,[31] but high doses are known to cause nicotine poisoning.[32]
.mw-parser-output .toclimit-2 .toclevel-1 ul,.mw-parser-output .toclimit-3 .toclevel-2 ul,.mw-parser-output .toclimit-4 .toclevel-3 ul,.mw-parser-output .toclimit-5 .toclevel-4 ul,.mw-parser-output .toclimit-6 .toclevel-5 ul,.mw-parser-output .toclimit-7 .toclevel-6 ul{display:none}
Contents
1 Uses
1.1 Medical
1.2 Pesticide
1.3 Enhancing performance
1.4 Recreational
2 Contraindications
3 Side effects
3.1 Sleep
3.2 Cardiovascular system
3.3 Cancer
3.4 Fetal development and breastfeeding
4 Overdose
4.1 Reinforcement disorders
4.2 Toxicity
5 Drug interactions
5.1 Pharmacodynamic
5.2 Pharmacokinetic
6 Pharmacology
6.1 Pharmacodynamics
6.1.1 Central nervous system
6.1.2 Sympathetic nervous system
6.1.3 Adrenal medulla
6.2 Pharmacokinetics
7 Chemistry
7.1 Occurrence
7.2 Biosynthesis
7.3 Detection in body fluids
8 History, society, and culture
8.1 Legal status
8.2 In media
9 Research
9.1 Central nervous system
9.2 Immune system
10 References
11 External links
Uses
Medical
A 21 mg patch applied to the left arm. The Cochrane Collaboration finds that nicotine replacement therapy increases a quitter's chance of success by 50% to 70%.[33][needs update]
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, inhalers, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence. Studies have found that these therapies increase the chance of success of quitting by 50 to 70%,[33] though reductions in the population as a whole have not been demonstrated.[34]
In contrast to recreational nicotine products, which have been designed to maximize the likelihood of addiction, nicotine replacement products (NRTs) are designed to minimize addictiveness.[32]:112 The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.[23]
Pesticide
Nicotine has been used as an insecticide since at least the 1690s, in the form of tobacco extracts[35] (although other components of tobacco also seem to have pesticide effects).[36] Nicotine pesticides have not been commercially available in the US since 2014,[37] and homemade pesticides are banned on organic crops[38] and counterrecommended for small gardeners.[39] Nicotine pesticides have been banned in the EU since 2009.[40] Foods are imported from countries in which nicotine pesticides are allowed, such as China, but foods may not exceed maximum nicotine levels.[40][41]Neonicotinoids, which are derived from and structurally similar to nicotine, are widely used as agricultural and veterinary pesticides as of 2016.[42][35]
In nicotine-producing plants, nicotine functions as an antiherbivory chemical; consequently, nicotine has been widely used as an insecticide,[43][14] and neonicotinoids, such as imidacloprid, are widely used.
Enhancing performance
Nicotine-containing products are sometimes used for the performance-enhancing effects of nicotine on cognition.[citation needed] A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory.[44] A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance;[45] among the nicotinic receptor subtypes, nicotine has the highest binding affinity at the α4β2 receptor (ki=1 nM), which is also the biological target that mediates nicotine's addictive properties.[46] Nicotine has potential beneficial effects, but it also has paradoxical effects, which may be due to the inverted U-shape of the dose-response curve or pharmacokinetic features.[47]
Recreational
Nicotine is used as a recreational drug.[48] It is widely used because it is highly addictive and hard to discontinue using it.[49] Nicotine is often used compulsively,[50] and dependence can develop within days.[50][51] Recreational drug users commonly use nicotine for its mood-altering effects.[23] Other recreational nicotine products include chewing tobacco,[citation needed]cigars,[52]cigarettes,[52]e-cigarettes,[53]snuff,[citation needed]pipe tobacco,[52] and snus.[citation needed]
Contraindications
According to the American Society of Health-System Pharmacists, nicotine in any form is contraindicated in individuals with a known hypersensitivity to nicotine and nicotine polacrilex gum is contraindicated in individuals with temporomandibular joint disease.[54]
Side effects
Nicotine is not harmless,[55] but it is safer than inhaled tobacco smoke.[56] As medicine, nicotine is used to help with quitting smoking and has good safety in this form.[26] The accepted medical position in 2007 was that nicotine itself poses few health risks, except among certain vulnerable groups[27] such as youth,[28] but the ideal course of action for smokers is to quit all nicotine use.[57] The common side effects from nicotine exposure are listed in the table below.
Route of administration |
Dosage form |
Associated side effects of nicotine |
Sources |
|---|---|---|---|
Buccal |
Nicotine gum |
Indigestion, nausea, hiccups, traumatic injury to oral mucosa or teeth, irritation or tingling of the mouth and throat, oral mucosal ulceration, jaw-muscle ache, burping, gum sticking to teeth, unpleasant taste, dizziness, lightheadedness, headache, and insomnia. |
[54] |
Buccal |
Lozenge |
Nausea, dyspepsia, flatulence, headache, and upper respiratory tract infections. |
[54] |
Transdermal |
Transdermal patch |
Application site reactions (i.e., pruritus, burning, or erythema), diarrhea, dyspepsia, abdominal pain, dry mouth, nausea, dizziness, nervousness or restlessness, headache, vivid dreams or other sleep disturbances, and irritability. |
[54][58] |
Intranasal |
Nasal spray |
Runny nose, nasopharyngeal and ocular irritation, watery eyes, sneezing, and cough. |
[54][59] |
| Oral inhalation |
Inhaler |
Dyspepsia, oropharyngeal irritation (e.g., coughing, irritation of the mouth and throat), rhinitis, and headache. |
[54][60] |
| All (nonspecific) |
Peripheral vasoconstriction, tachycardia (i.e., fast heart rate), elevated blood pressure, and increased alertness and cognitive performance. |
[54][59] |
|
Sleep
Possible side effects of nicotine.[61]
Nicotine reduces the amount of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and total sleep time in healthy nonsmokers given nicotine via a transdermal patch, and the reduction is dose-dependent.[62] Acute nicotine intoxication has been found to significantly reduce total sleep time and increase REM latency, sleep onset latency, and non-rapid eye movement (NREM) stage 2 sleep time.[62][63]
Cardiovascular system
A 2012 Cochrane review found that nicotine replacement therapy does not increase the risk of adverse cardiovascular events in smokers who have a history of cardiovascular disease.[64][needs update]
Cancer
Although nicotine does not cause cancer in humans,[29] it is unclear whether it functions as a tumor promoter as of 2012[update].[65] Low levels of nicotine stimulate cell proliferation, while high levels are cytotoxic.[66] Nicotine increases cholinergic signaling and adrenergic signaling in colon cancer cells,[67] thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-lipoxygenase (5-LOX), and epidermal growth factor (EGF). Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization.[68][69] 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).[70] In cancer cells, nicotine promotes the epithelial–mesenchymal transition which makes the cancer cells more resistant to drugs that treat cancer.[71]
Fetal development and breastfeeding
Nicotine has been shown to produce birth defects in some animal species, but not others;[30] consequently, it is considered to be a possible teratogen in humans.[30] In animal studies that resulted in birth defects, researchers found that nicotine negatively affects fetal brain development and pregnancy outcomes;[30][32] the negative effects on early brain development are associated with abnormalities in brain metabolism and neurotransmitter system function.[72] Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.[73]
Some evidence suggests that in utero nicotine exposure influences the occurrence of certain conditions later in life, including type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.[26]
Overdose
It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013 that there are no significant safety concerns associated with the use of more than one form of over-the-counter (OTC) nicotine replacement therapy at the same time, or using OTC NRT at the same time as another nicotine-containing product, like cigarettes.[74] The median lethal dose of nicotine in humans is unknown.[31][19] Nevertheless, nicotine has a relatively high toxicity in comparison to many other alkaloids such as caffeine, which has an LD50 of 127 mg/kg when administered to mice.[75] At sufficiently high doses, it is associated with nicotine poisoning,[32] which, while common in children, rarely results in significant morbidity or death.[30]
The initial symptoms of a nicotine overdose typically include nausea, vomiting, diarrhea, hypersalivation, abdominal pain, tachycardia (rapid heart rate), hypertension (high blood pressure), tachypnea (rapid breathing), headache, dizziness, pallor (pale skin), auditory or visual disturbances, and perspiration, followed shortly after by marked bradycardia (slow heart rate), bradypnea (slow breathing), and hypotension (low blood pressure).[30] Respiratory stimulation (i.e., tachypnea) is one of the primary signs of nicotine poisoning.[30] At sufficiently high doses, somnolence (sleepiness or drowsiness), confusion, syncope (loss of consciousness from fainting), shortness of breath, marked weakness, seizures, and coma may occur.[5][30] Lethal nicotine poisoning rapidly produces seizures, and death – which may occur within minutes – is believed to be due to respiratory paralysis.[30]
Reinforcement disorders
ΔFosB accumulation from excessive drug use Top: this depicts the initial effects of high dose exposure to an addictive drug on gene expression in the nucleus accumbens for various Fos family proteins (i.e., c-Fos, FosB, ΔFosB, Fra1, and Fra2). Bottom: this illustrates the progressive increase in ΔFosB expression in the nucleus accumbens following repeated twice daily drug binges, where these phosphorylated (35–37 kilodalton) ΔFosB isoforms persist in the D1-type medium spiny neurons of the nucleus accumbens for up to 2 months.[76][77] |
Nicotine is highly addictive.[15][16][17]Nicotine dependence involves aspects of both psychological dependence and physical dependence, since discontinuation of extended use has been shown to produce both affective (e.g., anxiety, irritability, craving, anhedonia) and somatic (mild motor dysfunctions such as tremor) withdrawal symptoms.[1] Withdrawal symptoms peak in one to three days[78] and can persist for several weeks.[79] Some people experience symptoms for 6 months or longer.[80]
Normal between-cigarettes discontinuation, in unrestricted smokers, causes mild but measurable nicotine withdrawal symptoms.[81] These include mildly worse mood, stress, anxiety, cognition, and sleep, all of which briefly return to normal with the next cigarette.[81] Smokers have worse mood than they would have if they were not nicotine-dependent; they experience normal moods only immediately after smoking.[25] Nicotine dependence is associated with poor sleep quality and shorter sleep duration among smokers.[82][83]
In dependent smokers, withdrawal causes impairments in memory and attention, and smoking during withdrawal returns these cognitive abilities to pre-withdrawal levels.[84] The temporarily increased cognitive levels of smokers after inhaling smoke are offset by periods of cognitive decline during nicotine withdrawal.[81] Therefore, the overall daily cognitive levels of smokers and non-smokers are roughly similar.[81]
Nicotine activates the mesolimbic pathway and induces long-term ΔFosB expression (i.e., produces phosphorylated ΔFosB isoforms) in the nucleus accumbens when inhaled or injected frequently or at high doses, but not necessarily when ingested.[85][86][87] Consequently, high daily exposure (possibly excluding oral route) to nicotine can cause ΔFosB overexpression in the nucleus accumbens, resulting in nicotine addiction.[85][86]
Toxicity
Today nicotine is less commonly used in agricultural insecticides, which was a main source of poisoning. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness,[30] accidental ingestion of tobacco or tobacco products, or ingestion of nicotine-containing plants.[88][89][90] People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by dermal exposure to wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco.[88][91] People can be exposed to nicotine in the workplace by breathing it in, skin absorption, swallowing it, or eye contact. The Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for nicotine exposure in the workplace as 0.5 mg/m3 skin exposure over an 8-hour workday. The US National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 0.5 mg/m3 skin exposure over an 8-hour workday. At environmental levels of 5 mg/m3, nicotine is immediately dangerous to life and health.[92]
Drug interactions
Pharmacodynamic
- Potential interaction with sympathomimetic drugs (adrenergic agonists) and sympatholytic drugs (alpha-blockers and beta-blockers).[54]
Pharmacokinetic
Nicotine and cigarette smoke both induce the expression of liver enzymes (e.g., certain cytochrome P450 proteins) which metabolize drugs, leading to the potential for alterations in drug metabolism.[54]
Smoking cessation may decrease the metabolism of acetaminophen, beta-blockers, caffeine, oxazepam, pentazocine, propoxyphene, theophylline, and tricyclic antidepressants, leading to higher plasma concentrations of these drugs.[54]
- Possible alteration of nicotine absorption through the skin from the transdermal nicotine patch by drugs that cause vasodilation or vasoconstriction.[54]
- Possible alteration of nicotine absorption through the nasal cavity from the nicotine nasal spray by nasal vasoconstrictors (e.g., xylometazoline).[54]
- Possible alteration of nicotine absorption through oral mucosa from nicotine gum and lozenges by food and drink that modify salivary pH.[54]
Pharmacology
Pharmacodynamics
Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs),[8][9] except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.[8]
Central nervous system
Effect of nicotine on dopaminergic neurons.
By binding to nicotinic acetylcholine receptors in the brain, nicotine elicits its psychoactive effects and increases the levels of several neurotransmitters in various brain structures – acting as a sort of "volume control."[93][94] Nicotine has a higher affinity for nicotinic receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis.[95] Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.[96] Nicotine is unusual in comparison to most drugs, as its profile changes from stimulant to sedative with increasing dosages, a phenomenon known as "Nesbitt's paradox" after the doctor who first described it in 1969.[97][98] At very high doses it dampens neuronal activity.[99] Nicotine induces both behavioral stimulation and anxiety in animals.[5] Research into nicotine's most predominant metabolite, cotinine, suggests that some of nicotine's psychoactive effects are mediated by cotinine.[100]
Nicotine activates nicotinic receptors (particularly α4β2 nicotinic receptors) on neurons that innervate the ventral tegmental area and within the mesolimbic pathway where it appears to cause the release of dopamine.[101][102] This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the ventral tegmental area.[102] Nicotine also appears to induce the release of endogenous opioids that activate opioid pathways in the reward system, since naltrexone – an opioid receptor antagonist – blocks nicotine self-administration.[101] These actions are largely responsible for the strongly reinforcing effects of nicotine, which often occur in the absence of euphoria;[101] however, mild euphoria from nicotine use can occur in some individuals.[101] Chronic nicotine use inhibits class I and II histone deacetylases in the striatum, where this effect plays a role in nicotine addiction.[103][104]
Sympathetic nervous system
Effect of nicotine on chromaffin cells.
Nicotine also activates the sympathetic nervous system,[105] acting via splanchnic nerves to the adrenal medulla, stimulating 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.
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.[106]
Pharmacokinetics
Urinary metabolites of nicotine, quantified as average percentage of total urinary nicotine.[107]
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.[108] The elimination half-life of nicotine in the body is around two hours.[109] Nicotine is primarily excreted in urine and urinary concentrations vary depending upon urine flow rate and urine pH.[5]
The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine,[110] suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation".
Nicotine has a half-life of 1–2 hours. Cotinine is an active metabolite of nicotine that remains in the blood with a half-life of 18–20 hours, making it easier to analyze.[111]
Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6) and FMO3, which selectively metabolizes (S)-nicotine. A major metabolite is cotinine. Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.[112] Under some conditions, other substances may be formed such as myosmine.[113]
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.[114]
Chemistry
NFPA 704 fire diamond | |
|---|---|
 1 4 0 The fire diamond hazard sign for nicotine.[115] |
Nicotine is a hygroscopic, colorless to yellow-brown, oily liquid, that is readily soluble in alcohol, ether or light petroleum. It is miscible with water in its base form between 60 °C and 210 °C. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water-soluble. Its flash point is 95 °C and its auto-ignition temperature is 244 °C.[116] Nicotine is readily volatile (vapor pressure 5.5 ㎩ at 25 ℃) and dibasic (Kb1=1×10⁻⁶, Kb2=1×10⁻¹¹).[117] On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (vitamin B3), and methylamine.[118]
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.[119] The salts of (+)-nicotine are usually dextrorotatory. The hydrochloride and sulphate salts become optically inactive if heated in a closed vessel above 180 °C.[118]
Anabasine is a structural isomer of nicotine, as both compounds have the molecular formula C10H14N2.
Occurrence
Nicotine is a natural product of tobacco, occurring in the leaves of Nicotiana tabacum in a range of 0.5 to 7.5% depending on variety.[120] Nicotine is also found in the leaves of Nicotiana rustica, in amounts of 2–14%; in Duboisia hopwoodii; and in Asclepias syriaca.[117]
Nicotine also naturally occurs in smaller amounts (varying from 2–7 µg/kg, or 20–70 millionths of a percent wet weight[12]) in Solanaceaein plants from the family Solanaceae (such as potatoes, tomatoes, eggplant, and peppers[12]).[121]
The amounts of nicotine of tomato varieties lowered substantially as the fruits ripened.[12] Nicotine content in tea leaves is greatly inconsistent and in some cases considerably greater than in the Solanaceae fruits.[12] A 1999 report found "In some papers it is suggested that the contribution of dietary nicotine intake is significant when compared with exposure to ETS [environmental tobacco smoke] or by active smoking of small numbers of cigarettes. Others consider the dietary intake to be negligible unless inordinately large amounts of specific vegetables are consumed."[12] The amount of nicotine eaten per day is roughly around 1.4 and 2.25 µg/day at the 95th percentile.[12] These numbers may be low due to insufficient food intake data.[12] Since the amounts of nicotine from the Solanum family including potato, tomato, eggplant, and from the Capsicum family vary in the parts per billion, they are tough to measure.[122]
Biosynthesis
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.[123][124] 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 with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form niacin mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of nicotinamide by the enzyme nicotinamidase.[citation needed]
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.[citation needed]
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.[125]
Detection in body fluids
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.[126][127] Nicotine use is not regulated in competitive sports programs.[128]
History, society, and culture
Nicotine was originally isolated from the tobacco plant in 1828 by chemists Wilhelm Heinrich Posselt and Karl Ludwig Reimann from Germany, who believed it was a poison.[129][130] Its chemical empirical formula was described by Melsens in 1843,[131] its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893,[132][133][134][clarification needed] and it was first synthesized by Amé Pictet and A. Rotschy in 1904.[135]
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, presented to the French King,[136] and who promoted their medicinal use. Smoking was believed to protect against illness, particularly the plague.[136]
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 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.[14]
The nicotine content of popular American-brand cigarettes has increased over time, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005.[137]
Legal status
In the United States, nicotine products and Nicotine Replacement Therapy products like Nicotrol are only available to persons 18 and above; proof of age is required; not for sale in vending machine or from any source where proof of age cannot be verified. In some states[where?], these products are only available to persons over the age of 21.[medical citation needed][where?]
In the European Union, the minimum age to purchase nicotine products is 18, excepting the United Kingdom where the minimum age is 16. However, there is no minimum age requirement to use tobacco or nicotine products.[138]
In media
 An image showing Nick O'Teen fleeing from Superman, Comic Vine |
In some anti-smoking literature, the harm that tobacco smoking and nicotine addiction does is personified as Nick O'Teen, represented as a humanoid with some aspect of a cigarette or cigarette butt about him or his clothes and hat.[139] Nick O'Teen was a villain that was created for the Health Education Council.[139]
Research
Central nervous system
While acute/initial nicotine intake causes activation of neuronal nicotine receptors, chronic low doses of nicotine use leads to desensitisation of those receptors (due to the development of tolerance) and results in an antidepressant effect, with early research showing low dose nicotine patches could be an effective treatment of major depressive disorder in non-smokers.[140]
Though tobacco smoking is associated with an increased risk of Alzheimer's disease,[141] there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease.[142]
Immune system
Immune cells of both the Innate immune system and adaptive immune systems frequently express the α2, α5, α6, α7, α9, and α10 subunits of nicotinic acetylcholine receptors.[143] Evidence suggests that nicotinic receptors which contain these subunits are involved in the regulation of immune function.[143]
References
^ abc D'Souza MS, Markou A (July 2011). "Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments". Addiction Science & Clinical Practice. 6 (1): 4–16. PMC 3188825. PMID 22003417.Withdrawal symptoms upon cessation of nicotine intake: Chronic nicotine use induces neuroadaptations in the brain’s reward system that result in the development of nicotine dependence. Thus, nicotine-dependent smokers must continue nicotine intake to avoid distressing somatic and affective withdrawal symptoms. Newly abstinent smokers experience symptoms such as depressed mood, anxiety, irritability, difficulty concentrating, craving, bradycardia, insomnia, gastrointestinal discomfort, and weight gain (Shiffman and Jarvik, 1976; Hughes et al., 1991). Experimental animals, such as rats and mice, exhibit a nicotine withdrawal syndrome that, like the human syndrome, includes both somatic signs and a negative affective state (Watkins et al., 2000; Malin et al., 2006). The somatic signs of nicotine withdrawal include rearing, jumping, shakes, abdominal constrictions, chewing, scratching, and facial tremors. The negative affective state of nicotine withdrawal is characterized by decreased responsiveness to previously rewarding stimuli, a state called anhedonia.
.mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"""""""'""'"}.mw-parser-output .citation .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/4/4c/Wikisource-logo.svg/12px-Wikisource-logo.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
^ Cosci F, Pistelli F, Lazzarini N, Carrozzi L (2011). "Nicotine dependence and psychological distress: outcomes and clinical implications in smoking cessation". Psychology Research and Behavior Management. 4: 119–28. doi:10.2147/prbm.s14243. PMC 3218785. PMID 22114542.
^ Hollinger MA (19 October 2007). Introduction to Pharmacology (Third ed.). Abingdon: CRC Press. pp. 222–223. ISBN 978-1-4200-4742-4.
^ ab "Nicotine". PubChem Compound Database. United States National Library of Medicine – National Center for Biotechnology Information. 16 February 2019. Retrieved 19 March 2019.
^ abcde Landoni JH. "Nicotine (PIM)". INCHEM. International Programme on Chemical Safety. Retrieved 29 January 2019.
^ "Nicotine: Clinical data". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 19 March 2019.Used as an aid to smoking cessation and for the relief of nicotine withdrawal symptoms.
^ Abou-Donia M (5 February 2015). Mammalian Toxicology. John Wiley & Sons. pp. 587–. ISBN 978-1-118-68285-2.
^ abcd "Nicotinic acetylcholine receptors: Introduction". IUPHAR Database. International Union of Basic and Clinical Pharmacology. Retrieved 1 September 2014.
^ ab Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 9: Autonomic Nervous System". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 234. ISBN 9780071481274.Nicotine ... is a natural alkaloid of the tobacco plant. Lobeline is a natural alkaloid of Indian tobacco. Both drugs are agonists are nicotinic cholinergic receptors ...
^ Kishioka S, Kiguchi N, Kobayashi Y, Saika F (2014). "Nicotine effects and the endogenous opioid system". Journal of Pharmacological Sciences. 125 (2): 117–24. doi:10.1254/jphs.14R03CP. PMID 24882143.
^ "Smoking and Tobacco Control Monograph No. 9" (PDF). Retrieved 19 December 2012.
^ abcdefghij Siegmund B, Leitner E, Pfannhauser W (August 1999). "Determination of the nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake". Journal of Agricultural and Food Chemistry. 47 (8): 3113–20. doi:10.1021/jf990089w. PMID 10552617.
^ Rodgman A, Perfetti TA (2009). The chemical components of tobacco and tobacco smoke. Boca Raton, FL: CRC Press. ISBN 978-1-4200-7883-1. LCCN 2008018913.
[page needed]
^ abc Ujváry I (1999). "Nicotine and Other Insecticidal Alkaloids". In Yamamoto I, Casida J. Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor. Tokyo: Springer-Verlag. pp. 29–69.
^ ab Grana R, Benowitz N, Glantz SA (May 2014). "E-cigarettes: a scientific review". Circulation. 129 (19): 1972–86. doi:10.1161/circulationaha.114.007667. PMC 4018182. PMID 24821826.
^ abc Holbrook BD (June 2016). "The effects of nicotine on human fetal development". Birth Defects Research. Part C, Embryo Today. 108 (2): 181–92. doi:10.1002/bdrc.21128. PMID 27297020.
^ ab Siqueira LM (January 2017). "Nicotine and Tobacco as Substances of Abuse in Children and Adolescents". Pediatrics. 139 (1): e20163436. doi:10.1542/peds.2016-3436. PMID 27994114.
^ Sajja RK, Rahman S, Cucullo L (March 2016). "Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress". Journal of Cerebral Blood Flow and Metabolism. 36 (3): 539–54. doi:10.1177/0271678X15616978. PMC 4794105. PMID 26661236.
^ ab Mayer B (January 2014). "How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century". Archives of Toxicology. 88 (1): 5–7. doi:10.1007/s00204-013-1127-0. PMC 3880486. PMID 24091634.
^ Caponnetto P, Campagna D, Papale G, Russo C, Polosa R (February 2012). "The emerging phenomenon of electronic cigarettes". Expert Review of Respiratory Medicine. 6 (1): 63–74. doi:10.1586/ers.11.92. PMID 22283580.
^ Jain R, Mukherjee K, Balhara YP (April 2008). "The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review". Yonsei Medical Journal. 49 (2): 175–88. doi:10.3349/ymj.2008.49.2.175. PMC 2615322. PMID 18452252.
^ Miyasato K (March 2013). "[Psychiatric and psychological features of nicotine dependence]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 71 (3): 477–81. PMID 23631239.
^ abc Parrott AC (July 2015). "Why all stimulant drugs are damaging to recreational users: an empirical overview and psychobiological explanation" (PDF). Human Psychopharmacology. 30 (4): 213–24. doi:10.1002/hup.2468. PMID 26216554.
^ Parrott AC (March 2006). "Nicotine psychobiology: how chronic-dose prospective studies can illuminate some of the theoretical issues from acute-dose research" (PDF). Psychopharmacology. 184 (3–4): 567–76. doi:10.1007/s00213-005-0294-y. PMID 16463194.
^ abc Parrott AC (April 2003). "Cigarette-Derived Nicotine is not a Medicine" (PDF). The World Journal of Biological Psychiatry. 4 (2): 49–55. doi:10.3109/15622970309167951. ISSN 1562-2975.Regular smokers need nicotine to remain feeling normal, and suffer from adverse moods without it... Smoking only generates mood changes in nicotine-deprived smokers, but these only represent the restoration of normal moods. When non-deprived smokers have a cigarette, their mood ratings remain unaltered... When smokers completed a brief mood self-rating for every cigarette over the day, normal moods were reported immediately after smoking, moods deteriorated in between cigarettes, and were normalized by the next cigarette (Parrott 1994)... Thus smoke inhalation in an abstinent smoker restores 'pleasure' to normal levels
^ abc Schraufnagel DE, Blasi F, Drummond MB, Lam DC, Latif E, Rosen MJ, Sansores R, Van Zyl-Smit R (September 2014). "Electronic cigarettes. A position statement of the forum of international respiratory societies". American Journal of Respiratory and Critical Care Medicine. 190 (6): 611–8. doi:10.1164/rccm.201407-1198PP. PMID 25006874.
^ ab de Andrade M, Hastings G. "Tobacco Harm Reduction and Nicotine Containing Products" (PDF). Cancer Research UK. Cancer Research UK. p. 8. Retrieved 10 March 2016.
^ ab Schraufnagel DE (2015). "Electronic Cigarettes: Vulnerability of Youth". Pediatr Allergy Immunol Pulmonol. 28 (1): 2–6. doi:10.1089/ped.2015.0490. PMC 4359356. PMID 25830075.CS1 maint: Uses authors parameter (link)
^ ab "Does nicotine cause cancer?". European Code Against Cancer. World Health Organization – International Agency for Research on Cancer. Retrieved 23 January 2019.
^ abcdefghijk "Nicotine". United States National Library of Medicine – Toxicology Data Network. Hazardous Substances Data Bank. Retrieved 23 January 2019.
^ ab "Nicotine". European Chemicals Agency: Committee for Risk Assessment. September 2015. Retrieved 23 January 2019.
^ abcd National Center for Chronic Disease Prevention Health Promotion (US) Office on Smoking Health (2014). "The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, Chapter 5 – Nicotine" (PDF). Surgeon General of the United States: 107–138. PMID 24455788.
^ ab Stead LF, Perera R, Bullen C, Mant D, Lancaster T (January 2008). Stead LF, ed. "Nicotine replacement therapy for smoking cessation". The Cochrane Database of Systematic Reviews (1): CD000146. doi:10.1002/14651858.CD000146.pub3. PMID 18253970.
^ Pierce JP, Cummins SE, White MM, Humphrey A, Messer K (April 2012). "Nicotine Replacement for Smoking Cessation: Do We Need to Change Policy?". Annual Review of Public Health. 33: 341–56. doi:10.1146/annurev-publhealth-031811-124624. PMID 22224888.
^ ab Tomizawa M, Casida JE (2005). "Neonicotinoid insecticide toxicology: mechanisms of selective action" (PDF). Annual Review of Pharmacology and Toxicology. 45: 247–68. doi:10.1146/annurev.pharmtox.45.120403.095930. PMID 15822177.
^ "Tobacco and its evil cousin nicotine are good as a pesticide – American Chemical Society". American Chemical Society. Retrieved 29 October 2018.
^ USEPA (3 June 2009). "Nicotine; Product Cancellation Order". Federal Register: 26695–26696. Retrieved 8 April 2012.
^ US Code of Federal Regulations. 7 CFR 205.602 – Nonsynthetic substances prohibited for use in organic crop production
^ Tharp C (5 September 2014). "Safety for Homemade Remedies for Pest Control" (PDF). Montana Pesticide Bulletin. Montana State University. Retrieved 29 October 2018.
^ ab Michalski B, Herrmann M, Solecki R (July 2017). "[How does a pesticide residue turn into a contaminant?]". Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz (in German). 60 (7): 768–773. doi:10.1007/s00103-017-2556-3. PMID 28508955.
^ European Food Safety Authority (7 May 2009). "Potential risks for public health due to the presence of nicotine in wild mushrooms". EFSA Journal. 7 (5): 286r. doi:10.2903/j.efsa.2009.286r.
^ Abreu-Villaça Y, Levin ED (February 2017). "Developmental neurotoxicity of succeeding generations of insecticides". Environment International. 99: 55–77. doi:10.1016/j.envint.2016.11.019. PMC 5285268. PMID 27908457.
^ Rodgman A, Perfetti TA (2009). The chemical components of tobacco and tobacco smoke. Boca Raton, FL: CRC Press. ISBN 978-1-4200-7883-1. LCCN 2008018913.
[page needed]
^ Heishman SJ, Kleykamp BA, Singleton EG (July 2010). "Meta-analysis of the acute effects of nicotine and smoking on human performance". Psychopharmacology. 210 (4): 453–69. doi:10.1007/s00213-010-1848-1. PMC 3151730. PMID 20414766.
^ Sarter M (August 2015). "Behavioral-Cognitive Targets for Cholinergic Enhancement". Current Opinion in Behavioral Sciences. 4: 22–26. doi:10.1016/j.cobeha.2015.01.004. PMC 5466806. PMID 28607947.
^ "Nicotine: Biological activity". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 7 February 2016.Kis as follows; α2β4=9900nM [5], α3β2=14nM [1], α3β4=187nM [1], α4β2=1nM [4,6]. Due to the heterogeneity of nACh channels we have not tagged a primary drug target for nicotine, although the α4β2 is reported to be the predominant high affinity subtype in the brain which mediates nicotine addiction
^ Majdi A, Kamari F, Vafaee MS, Sadigh-Eteghad S (October 2017). "Revisiting nicotine's role in the ageing brain and cognitive impairment". Reviews in the Neurosciences. 28 (7): 767–781. doi:10.1515/revneuro-2017-0008. PMID 28586306.
^ Uban KA, Horton MK, Jacobus J, Heyser C, Thompson WK, Tapert SF, Madden PA, Sowell ER (August 2018). "Biospecimens and the ABCD study: Rationale, methods of collection, measurement and early data". Developmental Cognitive Neuroscience. 32: 97–106. doi:10.1016/j.dcn.2018.03.005. PMID 29606560.
^ Siqueira LM (January 2017). "Nicotine and Tobacco as Substances of Abuse in Children and Adolescents". Pediatrics. 139 (1): e20163436. doi:10.1542/peds.2016-3436. PMID 27994114.
^ ab Stolerman IP, Jarvis MJ (January 1995). "The scientific case that nicotine is addictive". Psychopharmacology. 117 (1): 2–10, discussion 14–20. doi:10.1007/BF02245088. PMID 7724697.
^ Wilder N, Daley C, Sugarman J, Partridge J (April 2016). "Nicotine without smoke: Tobacco harm reduction". UK: Royal College of Physicians. pp. 58, 125.
^ abc El Sayed KA, Sylvester PW (June 2007). "Biocatalytic and semisynthetic studies of the anticancer tobacco cembranoids". Expert Opinion on Investigational Drugs. 16 (6): 877–87. doi:10.1517/13543784.16.6.877. PMID 17501699.
^ Rahman MA, Hann N, Wilson A, Worrall-Carter L (2014). "Electronic cigarettes: patterns of use, health effects, use in smoking cessation and regulatory issues". Tobacco Induced Diseases. 12 (1): 21. doi:10.1186/1617-9625-12-21. PMC 4350653. PMID 25745382.
^ abcdefghijklmn "Nicotine". Drugs.com. American Society of Health-System Pharmacists. Retrieved 24 January 2019.
^ Morjaria JB, Mondati E, Polosa R (2017). "E-cigarettes in patients with COPD: current perspectives". International Journal of Chronic Obstructive Pulmonary Disease. 12: 3203–3210. doi:10.2147/COPD.S135323. PMC 5677304. PMID 29138548.
^ Mishra A, Chaturvedi P, Datta S, Sinukumar S, Joshi P, Garg A (2015). "Harmful effects of nicotine". Indian Journal of Medical and Paediatric Oncology. 36 (1): 24–31. doi:10.4103/0971-5851.151771. PMC 4363846. PMID 25810571.
^ Nicotine without smoke: Tobacco harm reduction. London: Royal College of Physicians. 2016. p. 151. ISBN 978-1-86016-600-6.
^ "Nicotine Transdermal Patch" (PDF). United States Food and Drug Administration. Retrieved 24 January 2019.
^ ab "Nicotrol NS" (PDF). United States Food and Drug Administration. Retrieved 24 January 2019.
^ "Nicotrol" (PDF). Pfizer. Retrieved 24 January 2019.
^ Detailed reference list is located on a separate image page.
^ ab Garcia AN, Salloum IM (October 2015). "Polysomnographic sleep disturbances in nicotine, caffeine, alcohol, cocaine, opioid, and cannabis use: A focused review". The American Journal on Addictions. 24 (7): 590–8. doi:10.1111/ajad.12291. PMID 26346395.
^ Boutrel B, Koob GF (September 2004). "What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications". Sleep. 27 (6): 1181–94. doi:10.1093/sleep/27.6.1181. PMID 15532213.
^ Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K, Lancaster T (November 2012). "Nicotine replacement therapy for smoking cessation". The Cochrane Database of Systematic Reviews. 11: CD000146. doi:10.1002/14651858.CD000146.pub4. PMID 23152200.
^ Cardinale A, Nastrucci C, Cesario A, Russo P (January 2012). "Nicotine: specific role in angiogenesis, proliferation and apoptosis". Critical Reviews in Toxicology. 42 (1): 68–89. doi:10.3109/10408444.2011.623150. PMID 22050423.
^ Sanner T, Grimsrud TK (2015). "Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review". Frontiers in Oncology. 5: 196. doi:10.3389/fonc.2015.00196. PMC 4553893. PMID 26380225.
This article incorporates text by Tore Sanner and Tom K. Grimsrud available under the CC BY 4.0 license.
^ Wong HP, Yu L, Lam EK, Tai EK, Wu WK, Cho CH (June 2007). "Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation". Toxicological Sciences. 97 (2): 279–87. doi:10.1093/toxsci/kfm060. PMID 17369603.
^ Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M (October 2003). "Nicotine enhances neovascularization and promotes tumor growth". Molecules and Cells. 16 (2): 143–6. PMID 14651253.
^ Ye YN, Liu ES, Shin VY, Wu WK, Luo JC, Cho CH (January 2004). "Nicotine promoted colon cancer growth via epidermal growth factor receptor, c-Src, and 5-lipoxygenase-mediated signal pathway". The Journal of Pharmacology and Experimental Therapeutics. 308 (1): 66–72. doi:10.1124/jpet.103.058321. PMID 14569062.
^ Davis R, Rizwani W, Banerjee S, Kovacs M, Haura E, Coppola D, Chellappan S (October 2009). Pao W, ed. "Nicotine promotes tumor growth and metastasis in mouse models of lung cancer". PLOS One. 4 (10): e7524. Bibcode:2009PLoSO...4.7524D. doi:10.1371/journal.pone.0007524. PMC 2759510. PMID 19841737.
^ Kothari AN, Mi Z, Zapf M, Kuo PC (2014). "Novel clinical therapeutics targeting the epithelial to mesenchymal transition". Clinical and Translational Medicine. 3: 35. doi:10.1186/s40169-014-0035-0. PMC 4198571. PMID 25343018.
^ Behnke M, Smith VC (March 2013). "Prenatal substance abuse: short- and long-term effects on the exposed fetus". Pediatrics. 131 (3): e1009–24. doi:10.1542/peds.2012-3931. PMID 23439891.
^ "State Health Officer's Report on E-Cigarettes: A Community Health Threat" (PDF). California Tobacco Control Program. California Department of Public Health. January 2015.
^ "Consumer Updates: Nicotine Replacement Therapy Labels May Change". FDA. 1 April 2013.
^ Toxicology and Applied Pharmacology. Vol. 44, Pg. 1, 1978.
^ Nestler EJ, Barrot M, Self DW (September 2001). "DeltaFosB: a sustained molecular switch for addiction". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11042–11046. doi:10.1073/pnas.191352698. PMC 58680. PMID 11572966.Although the ΔFosB signal is relatively long-lived, it is not permanent. ΔFosB degrades gradually and can no longer be detected in brain after 1–2 months of drug withdrawal ... Indeed, ΔFosB is the longest-lived adaptation known to occur in adult brain, not only in response to drugs of abuse, but to any other perturbation (that doesn't involve lesions) as well.
^ Nestler EJ (December 2012). "Transcriptional mechanisms of drug addiction". Clin. Psychopharmacol. Neurosci. 10 (3): 136–143. doi:10.9758/cpn.2012.10.3.136. PMC 3569166. PMID 23430970.The 35–37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens induces NFκB
^ Das S, Prochaska JJ (October 2017). "Innovative approaches to support smoking cessation for individuals with mental illness and co-occurring substance use disorders". Expert Review of Respiratory Medicine. 11 (10): 841–850. doi:10.1080/17476348.2017.1361823. PMC 5790168. PMID 28756728.
^ Heishman SJ, Kleykamp BA, Singleton EG (July 2010). "Meta-analysis of the acute effects of nicotine and smoking on human performance". Psychopharmacology. 210 (4): 453–69. doi:10.1007/s00213-010-1848-1. PMC 3151730. PMID 20414766.The significant effects of nicotine on motor abilities, attention, and memory likely represent true performance enhancement because they are not confounded by withdrawal relief. The beneficial cognitive effects of nicotine have implications for initiation of smoking and maintenance of tobacco dependence.
^ Baraona LK, Lovelace D, Daniels JL, McDaniel L (May 2017). "Tobacco Harms, Nicotine Pharmacology, and Pharmacologic Tobacco Cessation Interventions for Women". Journal of Midwifery & Women's Health. 62 (3): 253–269. doi:10.1111/jmwh.12616. PMID 28556464.
^ abcd Parrott AC (April 2003). "Cigarette-Derived Nicotine is not a Medicine" (PDF). The World Journal of Biological Psychiatry. 4 (2): 49–55. doi:10.3109/15622970309167951. ISSN 1562-2975.
^ Dugas EN, Sylvestre MP, O'Loughlin EK, Brunet J, Kakinami L, Constantin E, O'Loughlin J (February 2017). "Nicotine dependence and sleep quality in young adults". Addictive Behaviors. 65: 154–160. doi:10.1016/j.addbeh.2016.10.020. PMID 27816041.
^ Cohrs S, Rodenbeck A, Riemann D, Szagun B, Jaehne A, Brinkmeyer J, Gründer G, Wienker T, Diaz-Lacava A, Mobascher A, Dahmen N, Thuerauf N, Kornhuber J, Kiefer F, Gallinat J, Wagner M, Kunz D, Grittner U, Winterer G (May 2014). "Impaired sleep quality and sleep duration in smokers-results from the German Multicenter Study on Nicotine Dependence". Addiction Biology. 19 (3): 486–96. doi:10.1111/j.1369-1600.2012.00487.x. hdl:11858/00-001M-0000-0025-BD0C-B. PMID 22913370.
^ Bruijnzeel AW (May 2012). "Tobacco addiction and the dysregulation of brain stress systems". Neuroscience and Biobehavioral Reviews. 36 (5): 1418–41. doi:10.1016/j.neubiorev.2012.02.015. PMC 3340450. PMID 22405889.Discontinuation of smoking leads to negative affective symptoms such as depressed mood, increased anxiety, and impaired memory and attention...Smoking cessation leads to a relatively mild somatic withdrawal syndrome and a severe affective withdrawal syndrome that is characterized by a decrease in positive affect, an increase in negative affect, craving for tobacco, irritability, anxiety, difficulty concentrating, hyperphagia, restlessness, and a disruption of sleep. Smoking during the acute withdrawal phase reduces craving for cigarettes and returns cognitive abilities to pre-smoking cessation level
^ ab Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–43. PMC 3898681. PMID 24459410.
^ ab Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". The American Journal of Drug and Alcohol Abuse. 40 (6): 428–37. doi:10.3109/00952990.2014.933840. PMID 25083822.The knowledge of ΔFosB induction in chronic drug exposure provides a novel method for the evaluation of substance addiction profiles (i.e. how addictive they are). Xiong et al. used this premise to evaluate the potential addictive profile of propofol (119). Propofol is a general anaesthetic, however its abuse for recreational purpose has been documented (120). Using control drugs implicated in both ΔFosB induction and addiction (ethanol and nicotine), ...
Conclusions
ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a ‘‘molecular switch’’ (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124).
^ Marttila K, Raattamaa H, Ahtee L (July 2006). "Effects of chronic nicotine administration and its withdrawal on striatal FosB/DeltaFosB and c-Fos expression in rats and mice". Neuropharmacology. 51 (1): 44–51. doi:10.1016/j.neuropharm.2006.02.014. PMID 16631212.
^ ab Schep LJ, Slaughter RJ, Beasley DM (September 2009). "Nicotinic plant poisoning". Clinical Toxicology. 47 (8): 771–81. doi:10.1080/15563650903252186. PMID 19778187.
^ Smolinske SC, Spoerke DG, Spiller SK, Wruk KM, Kulig K, Rumack BH (January 1988). "Cigarette and nicotine chewing gum toxicity in children". Human Toxicology. 7 (1): 27–31. doi:10.1177/096032718800700105. PMID 3346035.
^ Furer V, Hersch M, Silvetzki N, Breuer GS, Zevin S (March 2011). "Nicotiana glauca (tree tobacco) intoxication--two cases in one family". Journal of Medical Toxicology. 7 (1): 47–51. doi:10.1007/s13181-010-0102-x. PMC 3614112. PMID 20652661.
^ Gehlbach SH, Williams WA, Perry LD, Woodall JS (September 1974). "Green-tobacco sickness. An illness of tobacco harvesters". JAMA. 229 (14): 1880–3. doi:10.1001/jama.1974.03230520022024. PMID 4479133.
^ "CDC – NIOSH Pocket Guide to Chemical Hazards – Nicotine". www.cdc.gov. Retrieved 20 November 2015.
^ Pomerleau OF, Pomerleau CS (1984). "Neuroregulators and the reinforcement of smoking: towards a biobehavioral explanation". Neuroscience and Biobehavioral Reviews. 8 (4): 503–13. doi:10.1016/0149-7634(84)90007-1. PMID 6151160.
^ Pomerleau OF, Rosecrans J (1989). "Neuroregulatory effects of nicotine". Psychoneuroendocrinology. 14 (6): 407–23. doi:10.1016/0306-4530(89)90040-1. PMID 2560221.
^ Katzung BG (2006). Basic and Clinical Pharmacology. New York: McGraw-Hill Medical. pp. 99–105.
^ Xiu X, Puskar NL, Shanata JA, Lester HA, Dougherty DA (March 2009). "Nicotine binding to brain receptors requires a strong cation-pi interaction". Nature. 458 (7237): 534–7. Bibcode:2009Natur.458..534X. doi:10.1038/nature07768. PMC 2755585. PMID 19252481.
^ Nesbitt P (1969). Smoking, physiological arousal, and emotional response. Unpublished doctoral dissertation, Columbia University.
^ Parrott AC (January 1998). "Nesbitt's Paradox resolved? Stress and arousal modulation during cigarette smoking" (PDF). Addiction. 93 (1): 27–39. CiteSeerX 10.1.1.465.2496. doi:10.1046/j.1360-0443.1998.931274.x. PMID 9624709.
^ Wadgave U, Nagesh L (July 2016). "Nicotine Replacement Therapy: An Overview". International Journal of Health Sciences. 10 (3): 425–35. PMC 5003586. PMID 27610066.
^ Grizzell JA, Echeverria V (October 2015). "New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine". Neurochemical Research. 40 (10): 2032–46. doi:10.1007/s11064-014-1359-2. PMID 24970109.
^ abcd Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, eds. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 369, 372–373. ISBN 9780071481274.
^ ab Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E (June 2011). "The role of the central ghrelin system in reward from food and chemical drugs". Molecular and Cellular Endocrinology. 340 (1): 80–7. doi:10.1016/j.mce.2011.02.017. hdl:2077/26318. PMID 21354264.This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area.
^ Levine A, Huang Y, Drisaldi B, Griffin EA, Pollak DD, Xu S, Yin D, Schaffran C, Kandel DB, Kandel ER (November 2011). "Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine". Science Translational Medicine. 3 (107): 107ra109. doi:10.1126/scitranslmed.3003062. PMC 4042673. PMID 22049069.
^ Volkow ND (November 2011). "Epigenetics of nicotine: another nail in the coughing". Science Translational Medicine. 3 (107): 107ps43. doi:10.1126/scitranslmed.3003278. PMC 3492949. PMID 22049068.
^ Yoshida T, Sakane N, Umekawa T, Kondo M (January 1994). "Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress". Physiology & Behavior. 55 (1): 53–7. doi:10.1016/0031-9384(94)90009-4. PMID 8140174.
^ Marieb EN, Hoehn K (2007). Human Anatomy & Physiology (7th Ed.). Pearson. pp. ?. ISBN 978-0-8053-5909-1.
[page needed]
^ Henningfield JE, Calvento E, Pogun S (2009). Nicotine Psychopharmacology. Springer. pp. 35, 37. ISBN 978-3-540-69248-5.
^ Le Houezec J (September 2003). "Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review". The International Journal of Tuberculosis and Lung Disease. 7 (9): 811–9. PMID 12971663.
^ Benowitz NL, Jacob P, Jones RT, Rosenberg J (May 1982). "Interindividual variability in the metabolism and cardiovascular effects of nicotine in man". The Journal of Pharmacology and Experimental Therapeutics. 221 (2): 368–72. PMID 7077531.
^ Russell MA, Jarvis M, Iyer R, Feyerabend C. Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J. 1980 April 5; 280(6219): 972–976.
^ Bhalala O (Spring 2003). "Detection of Cotinine in Blood Plasma by HPLC MS/MS". MIT Undergraduate Research Journal. 8: 45–50. Archived from the original on 24 December 2013.
^ Hukkanen J, Jacob P, Benowitz NL (March 2005). "Metabolism and disposition kinetics of nicotine". Pharmacological Reviews. 57 (1): 79–115. doi:10.1124/pr.57.1.3. PMID 15734728.
^ Petrick LM, Svidovsky A, Dubowski Y (January 2011). "Thirdhand smoke: heterogeneous oxidation of nicotine and secondary aerosol formation in the indoor environment". Environmental Science & Technology. 45 (1): 328–33. Bibcode:2011EnST...45..328P. doi:10.1021/es102060v. PMID 21141815. Lay summary – Chromatography Online.
^ Benowitz NL, Herrera B, Jacob P (September 2004). "Mentholated cigarette smoking inhibits nicotine metabolism". The Journal of Pharmacology and Experimental Therapeutics. 310 (3): 1208–15. doi:10.1124/jpet.104.066902. PMID 15084646.
^ "NFPA Hazard Rating Information for Common Chemicals". Archived from the original on 17 February 2015. Retrieved 15 March 2015.
^ "L-Nicotine Material Safety Data Sheet". Sciencelab.com, Inc.
^ ab Metcalf RL (2007), "Insect Control", Ullmann's Encyclopedia of Industrial Chemistry (7th ed.), Wiley, p. 9
^ ab Henry TA (1949). The Plant Alkaloids (PDF) (4th ed.). Philadelphia, Toronto: The Blakiston Company.
^ Gause GF (1941). "Chapter V: Analysis of various biological processes by the study of the differential action of optical isomers". In Luyet, B. J. Optical Activity and Living Matter. A series of monographs on general physiology. 2. Normandy, Missouri: Biodynamica.
^ "Tobacco (leaf tobacco)". Transportation Information Service.
^ Domino EF, Hornbach E, Demana T (August 1993). "The nicotine content of common vegetables". The New England Journal of Medicine. 329 (6): 437. doi:10.1056/NEJM199308053290619. PMID 8326992.
^ Moldoveanu SC, Scott WA, Lawson DM (2016). "Nicotine Analysis in Several Non-Tobacco Plant Materials". Beiträge zur Tabakforschung International/Contributions to Tobacco Research. 27 (2): 54–59. doi:10.1515/cttr-2016-0008. ISSN 1612-9237.
^ Lamberts BL, Dewey LJ, Byerrum RU (May 1959). "Ornithine as a precursor for the pyrrolidine ring of nicotine". Biochimica et Biophysica Acta. 33 (1): 22–6. doi:10.1016/0006-3002(59)90492-5. PMID 13651178.
^ Dawson RF, Christman DR, d'Adamo A, Solt ML, Wolf AP (1960). "The Biosynthesis of Nicotine from Isotopically Labeled Nicotinic Acids". Journal of the American Chemical Society. 82 (10): 2628–2633. doi:10.1021/ja01495a059.
^ Ashihara H, Crozier A, Komamine A (eds.). Plant metabolism and biotechnology. Cambridge: Wiley. ISBN 978-0-470-74703-2.
[page needed]
^ Benowitz NL, Hukkanen J, Jacob P (1 January 2009). "Nicotine Chemistry, Metabolism, Kinetics and Biomarkers". Nicotine Psychopharmacology. Handbook of Experimental Pharmacology. 192. pp. 29–60. doi:10.1007/978-3-540-69248-5_2. ISBN 978-3-540-69246-1. PMC 2953858. PMID 19184645.
^ Baselt RC (2014). Disposition of Toxic Drugs and Chemicals in Man (10th ed.). Biomedical Publications. pp. 1452–6. ISBN 978-0-9626523-9-4.
^ Mündel T, Jones DA (July 2006). "Effect of transdermal nicotine administration on exercise endurance in men". Experimental Physiology. 91 (4): 705–13. doi:10.1113/expphysiol.2006.033373. PMID 16627574.
^ Henningfield JE, Zeller M (March 2006). "Nicotine psychopharmacology research contributions to United States and global tobacco regulation: a look back and a look forward". Psychopharmacology. 184 (3–4): 286–91. doi:10.1007/s00213-006-0308-4. PMID 16463054.
^ Posselt W, Reimann L (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]. Magazin für Pharmacie (in German). 6 (24): 138–161.
^ Melsens L (1843). "Note sur la nicotine" [Note on nicotine]. Annales de Chimie et de Physique. third series (in French). 9: 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).]
^ Pinner A, Wolffenstein R (1891). "Ueber Nicotin" [About nicotine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 24: 1373–1377. doi:10.1002/cber.189102401242.
^ Pinner A (1893). "Ueber Nicotin. Die Constitution des Alkaloïds" [About nicotine: The Constitution of the Alkaloids]. Berichte der Deutschen Chemischen Gesellschaft (in German). 26: 292–305. doi:10.1002/cber.18930260165.
^ Pinner A (1893). "Ueber Nicotin. I. Mitteilung". Archiv der Pharmazie. 231 (5–6): 378–448. doi:10.1002/ardp.18932310508.
^ Pictet A, Rotschy A (1904). "Synthese des Nicotins" [Synthesis of nicotine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 37 (2): 1225–1235. doi:10.1002/cber.19040370206.
^ ab Dale MM, Ritter JM, Fowler RJ, Rang HP. Rang & Dale's Pharmacology (6th ed.). Churchill Livingstone. p. 598. ISBN 978-0-8089-2354-1.
^ Connolly GN, Alpert HR, Wayne GF, Koh H (October 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.
^ "21, 18, or 14: A look at the legal age for smoking around the world". Straits Times. Retrieved 1 March 2019.
^ ab Jacob, Micheal (1 March 1985). "Superman versus Nick O'Teen — a children's anti-smoking campaign". Health Education Journal. 44 (1): 15–18. doi:10.1177/001789698504400104.
^ Mineur YS, Picciotto MR (December 2010). "Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis". Trends in Pharmacological Sciences. 31 (12): 580–6. doi:10.1016/j.tips.2010.09.004. PMC 2991594. PMID 20965579.
^ Peters R, Poulter R, Warner J, Beckett N, Burch L, Bulpitt C (December 2008). "Smoking, dementia and cognitive decline in the elderly, a systematic review". BMC Geriatrics. 8: 36. doi:10.1186/1471-2318-8-36. PMC 2642819. PMID 19105840.
^ Henningfield JE, Zeller M (2009). "Nicotine Psychopharmacology: Policy and Regulatory". Nicotine Psychopharmacology. Handbook of Experimental Pharmacology. 192. pp. 511–34. doi:10.1007/978-3-540-69248-5_18. ISBN 978-3-540-69246-1. PMID 19184661.
^ ab Fujii T, Mashimo M, Moriwaki Y, Misawa H, Ono S, Horiguchi K, Kawashima K (2017). "Expression and Function of the Cholinergic System in Immune Cells". Frontiers in Immunology. 8: 1085. doi:10.3389/fimmu.2017.01085. PMC 5592202. PMID 28932225.
This article incorporates text by Tore Sanner and Tom K. Grimsrud available under the CC BY 4.0 license.
External links
 |
Wikimedia Commons has media related to Nicotine. |
Toxicology monograph for Nicotine from the Hazardous Substances Data Bank
Chemical Hazards monograph for Nicotine from the National Institute for Occupational Safety and Health
Laboratory Chemical Safety Summary for Nicotine from PubChem
Cigarettes | ||
|---|---|---|
| Types |
|
 |
| Components |
|
|
| Peripherals |
|
|
| Culture |
|
|
| Health issues |
|
|
| Related products |
|
|
| Tobacco industry |
|
|
| Government and the law |
|
|
| Lists |
|
|
| ||
Category
CommonsReinforcement disorders: Addiction and Dependence | |||||||
|---|---|---|---|---|---|---|---|
| Addiction |
|
||||||
| Dependence |
|
||||||
| Treatment and management |
|
||||||
| See also |
|
||||||
| |||||||
Portal
Comments
Post a Comment