Nicotine


Nicotine is a widely used stimulant and potent parasympathomimetic alkaloid that is naturally produced in the nightshade family of plants. It is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors, except at two nicotinic receptor subunits where it acts as a receptor antagonist.
Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco. Nicotine is also present at concentrations of millionths of a percent in the edible family Solanaceae, including potatoes, tomatoes, and eggplants, though sources disagree on whether this has any biological significance to human consumers. It functions as an antiherbivore chemical; consequently, nicotine was widely used as an insecticide in the past, and neonicotinoids, such as imidacloprid, are widely used.
Nicotine is highly addictive, unless used in slow-release forms. An average cigarette yields about 2 mg of absorbed nicotine.
Higher doses can be fatal. Nicotine addiction involves drug-reinforced behavior, compulsive use, and relapse following abstinence. Nicotine dependence involves tolerance, sensitization, physical dependence, and psychological dependence. Nicotine dependence causes distress. Nicotine withdrawal symptoms include depressed mood, stress, anxiety, irritability, difficulty concentrating, and sleep disturbances. Mild nicotine withdrawal symptoms are measurable in unrestricted smokers, who experience normal moods only as their blood nicotine levels peak, with each cigarette. On quitting, withdrawal symptoms worsen sharply, then gradually improve to a normal state.
Nicotine use as a tool for quitting smoking has a good safety history. Nicotine itself is associated with some health harms. Nicotine is potentially harmful to non-users. At low amounts, it has a mild analgesic effect. The Surgeon General of the United States indicates that nicotine does not cause cancer. However, nicotine can react in the mouth and stomach to form N-Nitrosonornicotine, a known type 1 carcinogen. Nicotine has been shown to produce birth defects in some animal species, but not others. It is considered a teratogen in humans. The median lethal dose of nicotine in humans is unknown, but high doses are known to cause nicotine poisoning.

Uses

Medical

The primary therapeutic use of nicotine is treating nicotine dependence to eliminate smoking and the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, inhalers, or nasal sprays to wean them off their dependence. A 2018 Cochrane Collaboration review found high quality evidence that all current forms of nicotine replacement therapy therapies increase the chances of successfully quitting smoking by, regardless of setting.
Combining nicotine patch use with a faster acting nicotine replacement, like gum or spray, improves the odds of treatment success. 4 mg versus 2 mg nicotine gum also increase the chances of success.
In contrast to recreational nicotine products, which have been designed to maximize the likelihood of addiction, nicotine replacement products are designed to minimize addictiveness. The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.

Pesticide

Nicotine has been used as an insecticide since at least the 1690s, in the form of tobacco extracts. Nicotine pesticides have not been commercially available in the US since 2014, and homemade pesticides are banned on organic crops and not recommended for small gardeners. Nicotine pesticides have been banned in the EU since 2009. Foods are imported from countries in which nicotine pesticides are allowed, such as China, but foods may not exceed maximum nicotine levels. Neonicotinoids, which are derived from and structurally similar to nicotine, are widely used as agricultural and veterinary pesticides as of 2016.
In nicotine-producing plants, nicotine functions as an antiherbivory chemical; consequently, nicotine has been widely used as an insecticide, and neonicotinoids, such as imidacloprid, are widely used.

Performance

Nicotine-containing products are sometimes used for the performance-enhancing effects of nicotine on cognition. 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. A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance; among the nicotinic receptor subtypes, nicotine has the highest binding affinity at the α4β2 receptor, which is also the biological target that mediates nicotine's addictive properties. 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.

Recreational

Nicotine is used as a recreational drug. It is widely used, highly addictive and hard to discontinue. Nicotine is often used compulsively, and dependence can develop within days. Recreational drug users commonly use nicotine for its mood-altering effects. Other recreational nicotine products include chewing tobacco,, cigars, cigarettes, e-cigarettes, snuff, pipe tobacco, and snus.

Contraindications

Nicotine use for tobacco cessation has few contraindications.
It is not known whether nicotine replacement therapy is effective for smoking cessation in adolescents, as of 2014. It is therefore not recommended to adolescents. It is not safe to use nicotine during pregnancy or breastfeeding, although it is safer than smoking; the desirability of NRT use in pregnancy is therefore debated.
Precautions are needed when using NRT in people who have had a myocardial infarction within two weeks, a serious or worsening angina pectoris, and/or a serious underlying arrhythmia. Using nicotine products during cancer treatment is counterrecommended, as nicotine promotes tumour growth, but temporary use of NRTs to quit smoking may be advised for harm reduction.
Nicotine gum is contraindicated in individuals with temporomandibular joint disease. People with chronic nasal disorders and severe reactive airway disease require additional precautions when using nicotine nasal sprays. Nicotine in any form is contraindicated in individuals with a known hypersensitivity to nicotine.

Adverse effects

Nicotine is classified as a poison. Exposure to nicotine causes many adverse health effects. The common side effects from nicotine exposure are listed in the table below. Serious adverse events due to the use of nicotine replacement therapy are extremely rare. At low amounts, it has a mild analgesic effect. At sufficiently high doses, nicotine may result in nausea, vomiting, diarrhea, salivation, bradyarrhythmia, and possibly seizures, hypoventilation, and death.

Sleep

Nicotine reduces the amount of rapid eye movement sleep, slow-wave sleep, and total sleep time in healthy nonsmokers given nicotine via a transdermal patch, and the reduction is dose-dependent. Acute nicotine intoxication has been found to significantly reduce total sleep time and increase REM latency, sleep onset latency, and non-rapid eye movement stage 2 sleep time. Depressive non-smokers experience mood improvements under nicotine administration, but then the withdrawal effect has a negative effect on both mood and sleep.

Cardiovascular system

A 2018 Cochrane review found that, in rare cases, nicotine replacement therapy can cause non-ischemic chest pain and heart palpitations. The same review indicated that nicotine replacement therapy does not increase the incidence of serious cardiac adverse events relative to controls.

Reinforcement disorders

Nicotine is highly addictive. Its addictiveness depends on how it is administered. Nicotine dependence involves aspects of both psychological dependence and physical dependence, since discontinuation of extended use has been shown to produce both affective and somatic withdrawal symptoms. Withdrawal symptoms peak in one to three days and can persist for several weeks. Some people experience symptoms for 6 months or longer.
Normal between-cigarettes discontinuation, in unrestricted smokers, causes mild but measurable nicotine withdrawal symptoms. These include mildly worse mood, stress, anxiety, cognition, and sleep, all of which briefly return to normal with the next cigarette. Smokers have worse mood than they would have if they were not nicotine-dependent; they experience normal moods only immediately after smoking. Nicotine dependence is associated with poor sleep quality and shorter sleep duration among smokers.
In dependent smokers, withdrawal causes impairments in memory and attention, and smoking during withdrawal returns these cognitive abilities to pre-withdrawal levels. The temporarily increased cognitive levels of smokers after inhaling smoke are offset by periods of cognitive decline during nicotine withdrawal. Therefore, the overall daily cognitive levels of smokers and non-smokers are roughly similar.
Nicotine activates the mesolimbic pathway and induces long-term ΔFosB expression in the nucleus accumbens when inhaled or injected frequently or at high doses, but not necessarily when ingested. Consequently, high daily exposure to nicotine can cause ΔFosB overexpression in the nucleus accumbens, resulting in nicotine addiction.

Cancer

Although nicotine itself does not cause cancer in humans, it is unclear whether it functions as a tumor promoter as of 2012. A 2018 report by the National Academies of Sciences, Engineering, and Medicine concludes, "hile it is biologically plausible that nicotine can act as a tumor promoter, the existing body of evidence indicates this is unlikely to translate into increased risk of human cancer."
Low levels of nicotine stimulate cell proliferation, while high levels are cytotoxic. Nicotine increases cholinergic signaling and adrenergic signaling in colon cancer cells, thereby impeding apoptosis, promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-lipoxygenase, and epidermal growth factor. Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization. Nicotine promotes lung cancer development and accelerates its proliferation, angiogenesis, migration, invasion and epithelial–mesenchymal transition, via its influence on nAChRs receptors, whose presence has been confirmed in lung cancer cells. In cancer cells, nicotine promotes the epithelial–mesenchymal transition which makes the cancer cells more resistant to drugs that treat cancer.
Nicotine can form carcinogenic Tobacco-specific nitrosamines through a nitrosation reaction. This occurs mostly in the curing and processing of tobacco. However, nicotine in the mouth and stomach can react to form N-Nitrosonornicotine, a known type 1 carcinogen, suggesting that consumption of non-tobacco forms of nicotine may still play a role in carcinogenesis.

Pregnancy and breastfeeding

Nicotine has been shown to produce birth defects in some animal species, but not others; consequently, it is considered to be a possible teratogen in humans. In animal studies that resulted in birth defects, researchers found that nicotine negatively affects fetal brain development and pregnancy outcomes; the negative effects on early brain development are associated with abnormalities in brain metabolism and neurotransmitter system function. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.
Nicotine exposure in utero is responsible for several complications of pregnancy and birth: pregnant women who smoke are at greater risk for both miscarriage and stillbirth and infants exposed to nicotine in utero tend to have lower birth weights. 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.

Overdose

It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration stated in 2013 that there are no significant safety concerns associated with the use of more than one form of over-the-counter nicotine replacement therapy at the same time, or using OTC NRT at the same time as another nicotine-containing product, like cigarettes. The median lethal dose of nicotine in humans is unknown. 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. At sufficiently high doses, it is associated with nicotine poisoning, which, while common in children rarely results in significant morbidity or death.
The initial symptoms of a nicotine overdose typically include nausea, vomiting, diarrhea, hypersalivation, abdominal pain, tachycardia, hypertension, tachypnea, headache, dizziness, pallor, auditory or visual disturbances, and perspiration, followed shortly after by marked bradycardia, bradypnea, and hypotension. Respiratory stimulation is one of the primary signs of nicotine poisoning. At sufficiently high doses, somnolence, confusion, syncope, shortness of breath, marked weakness, seizures, and coma may occur. Lethal nicotine poisoning rapidly produces seizures, and death – which may occur within minutes – is believed to be due to respiratory paralysis.

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, accidental ingestion of tobacco or tobacco products, or ingestion of nicotine-containing plants. People who harvest or cultivate tobacco may experience Green Tobacco Sickness, 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. 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 has set the legal 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 has set a recommended exposure limit 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.

Drug interactions

Pharmacodynamic

Nicotine and cigarette smoke both induce the expression of liver enzymes which metabolize drugs, leading to the potential for alterations in drug metabolism.

Pharmacodynamics

Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors, except at two nicotinic receptor subunits where it acts as a receptor antagonist.

Central nervous system

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". 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. Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes. 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. At very high doses it dampens neuronal activity. Nicotine induces both behavioral stimulation and anxiety in animals. Research into nicotine's most predominant metabolite, cotinine, suggests that some of nicotine's psychoactive effects are mediated by cotinine.
Nicotine activates nicotinic receptors on neurons that innervate the ventral tegmental area and within the mesolimbic pathway where it appears to cause the release of dopamine. This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the ventral tegmental area. Nicotine can modulate the firing rate of the ventral tegmental area neurons. 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. These actions are largely responsible for the strongly reinforcing effects of nicotine, which often occur in the absence of euphoria; however, mild euphoria from nicotine use can occur in some individuals. Chronic nicotine use inhibits class I and II histone deacetylases in the striatum, where this effect plays a role in nicotine addiction.

Sympathetic nervous system

Nicotine also activates the sympathetic nervous system, 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 into the bloodstream.

Adrenal medulla

By binding to ganglion type nicotinic receptors in the adrenal medulla, nicotine increases flow of adrenaline, 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 into the bloodstream. The release of epinephrine causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.

Pharmacokinetics

As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation. The elimination half-life of nicotine in the body is around two hours. Nicotine is primarily excreted in urine and urinary concentrations vary depending upon urine flow rate and urine pH.
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 on the blood concentration of nicotine, 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.
Nicotine is metabolized in the liver by cytochrome P450 enzymes and FMO3, which selectively metabolizes -nicotine. A major metabolite is cotinine. Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide. Under some conditions, other substances may be formed such as myosmine.
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.

Metabolism

Nicotine decreases hunger and food consumption. The majority of research shows that nicotine reduces body weight, but some researchers have found that nicotine may result in weight gain under specific types of eating habits in animal models. Nicotine effect on weight appears to result from nicotine's stimulation of α3β4 nAChR receptors located in the POMC neurons in the arcuate nucleus and subsequently the melanocortin system, especially the melatocortin-4 receptors on second-order neurons in the paraventricular nucleus of the hypothalamus, thus modulating feeding inhibition. POMC neurons are a precursor of the melanocortin system, a critical regulator of body weight and peripheral tissue such as skin and hair.

Chemistry

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 neutral amine base form between 60 °C and 210 °C. It is a dibasic nitrogenous base, having Kb1=1×10⁻⁶, Kb2=1×10⁻¹¹. It readily forms ammonium salts with acids that are usually solid and water-soluble. Its flash point is 95 °C and its auto-ignition temperature is 244 °C. Nicotine is readily volatile On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid, and methylamine.
Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of D=–166.4°. The dextrorotatory form, -nicotine is physiologically less active than -nicotine. -nicotine is more toxic than -nicotine. The salts of -nicotine are usually dextrorotatory; this conversion between levorotatory and dextrorotatory upon protonation is common among alkaloids. The hydrochloride and sulfate salts become optically inactive if heated in a closed vessel above 180 °C. Anabasine is a structural isomer of nicotine, as both compounds have the molecular formula.
Pod mod electronic cigarettes use nicotine in the form of a protonated nicotine, rather than free-base nicotine found in earlier generations.

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. Nicotine is also found in the leaves of Nicotiana rustica, in amounts of 2–14%; in Duboisia hopwoodii; and in Asclepias syriaca.
Nicotine also naturally occurs in smaller amounts in Solanaceaein plants from the family Solanaceae.
The amounts of nicotine of in tomatoes lowers substantially as the fruit ripens. Nicotine content in tea leaves is greatly inconsistent and in some cases considerably greater than in the Solanaceae fruits. 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 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." The amount of nicotine eaten per day is roughly around 1.4 and 2.25 µg/day at the 95th percentile. These numbers may be low due to insufficient food intake data. 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.

Biosynthesis

The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that comprise nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from niacin while the pyrrolidine is derived from N-methyl-Δ1-pyrrollidium cation. 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. This is followed by a condensation with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase to form niacin mononucleotide. The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of nicotinamide by the enzyme nicotinamidase.
The N-methyl-Δ1-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of ornithine by ornithine decarboxylase to produce putrescine. Putrescine is then converted into N-methyl putrescine via methylation by SAM catalyzed by putrescine N-methyltransferase. N-methylputrescine then undergoes deamination into 4-methylaminobutanal by the N-methylputrescine oxidase enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-Δ1-pyrrollidium cation.
The final step in the synthesis of nicotine is the coupling between N-methyl-Δ1-pyrrollidium cation and niacin. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of niacin into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-Δ1-pyrrollidium cation to form enantiomerically pure -nicotine.

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. Nicotine use is not regulated in competitive sports programs.

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. Its chemical empirical formula was described by Melsens in 1843, its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and it was first synthesized by Amé Pictet and A. Rotschy in 1904.
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, and who promoted their medicinal use. Smoking was believed to protect against illness, particularly the plague.
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.
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.

Legal status

In the United States, nicotine products and Nicotine Replacement Therapy products like Nicotrol are only available to persons 21 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, these products are only available to persons over the age of 21. Many states in the US have implemented a Tobacco 21 law for tobacco products, raising the minimum age from 18 to 21. As of 2019, the minimum age to use tobacco is 21 at the federal level.
In the European Union, the minimum age to purchase nicotine products is 18. However, there is no minimum age requirement to use tobacco or nicotine products.

In media

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. Nick O'Teen was a villain that was created for the Health Education Council.
Nicotine was often compared to caffeine in advertisements in the 1980s by the tobacco industry, and later in the 2010s by the electronic cigarettes industry, in an effort to reduce the stigmatization and the public perception of the risks associated with nicotine use.

Research

Central nervous system

While acute/initial nicotine intake causes activation of neuronal nicotine receptors, chronic low doses of nicotine use leads to desensitization of those receptors 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.
Though tobacco smoking is associated with an increased risk of Alzheimer's disease, there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease.
Smoking is associated with a decreased risk of Parkinson's Disease; however, it is unknown whether this is due to people with healthier brain dopaminergic reward centers being more likely to enjoy smoking and thus pick up the habit, nicotine directly acting as a neuroprotective agent, or other compounds in cigarette smoke acting as neuroprotective agents.

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. Evidence suggests that nicotinic receptors which contain these subunits are involved in the regulation of immune function.

Optopharmacology

A photoactivatable form of nicotine, which releases nicotine when exposed to ultraviolet light with certain conditions, has been developed for studying nicotinic acetylcholine receptors in brain tissue.

Oral health

Several in vitro studies have investigated the potential effects of nicotine on a range of oral cells. A recent systematic review concluded that nicotine was unlikely to be cytotoxic to oral cells in vitro in most physiological conditions but further research is needed. Understanding the potential role of nicotine in oral health has become increasingly important given the recent introduction of novel nicotine products and their potential role in helping smokers quit.