|Trade names||Nicorette, Nicotrol|
| Physical: low–moderate|
| Routes of|
|Inhalation; insufflation; oral – buccal, sublingual, and ingestion; transdermal; rectal|
|Metabolism||Primarily hepatic: CYP2A6, CYP2B6, FMO3, others|
|Elimination half-life||1-2 hours; 20 hours active metabolite|
|Excretion|| Renal, urine pH-dependent; |
10–20% (gum), 30% (inhaled); 10–30% (intranasal)
|ECHA InfoCard|| 100.000.177 |
|Chemical and physical data|
|Molar mass||162.23 g/mol g·mol−1|
|3D model (JSmol)|
|Melting point||−79 °C (−110 °F)|
|Boiling point||247 °C (477 °F)|
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.Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.
Stimulants is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate, and amphetamine. It is estimated that the percentage of the population that has abused amphetamine-type stimulants and cocaine combined is between 0.8% and 2.1%.
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations. Higher potency does not necessarily mean more side effects.
Alkaloids are a class of naturally occurring organic compounds that mostly contain basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar structure may also be termed alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and, more rarely, other elements such as chlorine, bromine, and phosphorus.
Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco. µg/kg (20–70 millionths of a percent wet weight) are found in the edible family Solanaceae, such as potatoes, tomatoes, and eggplant. Some research indicates that the contribution of nicotine obtained from food is substantial in comparison to inhalation of second-hand smoke. Others consider nicotine obtained from food to be trivial unless exceedingly high amounts of certain vegetables are eaten. 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.Usually consistent concentrations of nicotine varying from 2–7
In mathematics, a percentage is a number or ratio expressed as a fraction of 100. It is often denoted using the percent sign, "%", or the abbreviations "pct.", "pct"; sometimes the abbreviation "pc" is also used. A percentage is a dimensionless number.
In the metric system, a microgram or microgramme is a unit of mass equal to one millionth of a gram. The unit symbol is μg according to the International System of Units. In μg the prefix symbol for micro- is the Greek letter μ (Mu).
The kilogram or kilogramme is the base unit of mass in the International System of Units (SI). Until 20 May 2019, it remains defined by a platinum alloy cylinder, the International Prototype Kilogram, manufactured in 1889, and carefully stored in Saint-Cloud, a suburb of Paris. After 20 May, it will be defined in terms of fundamental physical constants.
Nicotine is highly addictive. mg of absorbed nicotine; high amounts can be harmful. Nicotine induces both behavioral stimulation and anxiety in animals. Nicotine addiction involves drug-reinforced behavior, compulsive use, and relapse following abstinence. Nicotine dependence involves tolerance, sensitization, physical dependence, and psychological dependence. Nicotine dependency 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.It is one of the most commonly abused drugs. An average cigarette yields about 2
A cigarette, also known colloquially as a fag in British English, is a narrow cylinder containing psychoactive material, usually tobacco, that is rolled into thin paper for smoking. Most cigarettes contain a "reconstituted tobacco" product known as "sheet", which consists of "recycled [tobacco] stems, stalks, scraps, collected dust, and floor sweepings", to which are added glue, chemicals and fillers; the product is then sprayed with nicotine that was extracted from the tobacco scraps, and shaped into curls. The cigarette is ignited at one end, causing it to smolder and allowing smoke to be inhaled from the other end, which is held in or to the mouth. Most modern cigarettes are filtered, although this does not make them safer. Cigarette manufacturers have described cigarettes as a drug administration system for the delivery of nicotine in acceptable and attractive form. Cigarettes are addictive and cause cancer, chronic obstructive pulmonary disease, heart disease, and other health problems.
Addiction is a brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences. Despite the involvement of a number of psychosocial factors, a biological process – one which is induced by repeated exposure to an addictive stimulus – is the core pathology that drives the development and maintenance of an addiction. The two properties that characterize all addictive stimuli are that they are reinforcing and intrinsically rewarding.
Physical dependence is a physical condition caused by chronic use of a tolerance forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids, and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.
Nicotine use as a tool for quitting smoking has a good safety history.The general medical position is that nicotine itself poses few health risks, except among certain vulnerable groups, such as youth. The International Agency for Research on Cancer indicates that nicotine does not cause cancer. 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. The median lethal dose of nicotine in humans is unknown, but high doses are known to cause nicotine poisoning.
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and coordinate research into the causes of cancer. It also collects and publishes surveillance data regarding the occurrence of cancer worldwide.
In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a measure of the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity.
Nicotine poisoning describes the symptoms of the toxic effects of nicotine following ingestion, inhalation, or skin contact. Nicotine poisoning can potentially be deadly, though serious or fatal overdoses are rare. Historically, most cases of nicotine poisoning have been the result of use of nicotine as an insecticide. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness, or due to unintended ingestion of tobacco or tobacco products or consumption of nicotine-containing plants.
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. A 2018 Cochrane Collaboration review found high quality evidence that all current forms of nicotine replacement therapy (gum, patch, lozenges, inhaler, and nasal spray) therapies increase the chances of successfully quitting smoking by 50–60%, regardless of setting.
Pharmacotherapy is therapy using pharmaceutical drugs, as distinguished from therapy using surgery, radiation, movement, or other modes. Among physicians, sometimes the term medical therapy refers specifically to pharmacotherapy as opposed to surgical or other therapy; for example, in oncology, medical oncology is thus distinguished from surgical oncology.
Smoking is a practice in which a substance is burned and the resulting smoke breathed in to be tasted and absorbed into the bloodstream. Most commonly the substance is the dried leaves of the tobacco plant which have been rolled into a small square of rice paper to create a small, round cylinder called a "cigarette". Smoking is primarily practiced as a route of administration for recreational drug use because the combustion of the dried plant leaves vaporizes and delivers active substances into the lungs where they are rapidly absorbed into the bloodstream and reach bodily tissue. In the case of cigarette smoking these substances are contained in a mixture of aerosol particles and gasses and include the pharmacologically active alkaloid nicotine; the vaporization creates heated aerosol and gas into a form that allows inhalation and deep penetration into the lungs where absorption into the bloodstream of the active substances occurs. In some cultures, smoking is also carried out as a part of various rituals, where participants use it to help induce trance-like states that, they believe, can lead them to spiritual enlightenment.
Nicotine gum is a type of chewing gum that delivers nicotine to the body. It is used as an aid in nicotine replacement therapy (NRT), a process for smoking cessation and quitting smokeless tobacco. The nicotine is delivered to the bloodstream via absorption by the tissues of the mouth.
Combining nicotine patch use with a faster acting nicotine replacement, like gum or spray, improves the odds of treatment success. mg versus 2 mg nicotine gum also increase the chances of success.4
A nicotine patch is a transdermal patch that releases nicotine into the body through the skin. It is used in nicotine replacement therapy (NRT), a process for smoking cessation. Endorsed and approved by the Food and Drug Administration (FDA), it is considered one of the safer NRTs available.
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. 112 The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.:
Nicotine has been used as an insecticide since at least the 1690s, in the form of tobacco extracts(although other components of tobacco also seem to have pesticide effects). Nicotine pesticides have not been commercially available in the US since 2014, and homemade pesticides are banned on organic crops and counterrecommended 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.
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. 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 (ki=1 nM), 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.
Nicotine is used as a recreational drug. [ citation needed ] cigars, cigarettes, e-cigarettes, snuff,[ citation needed ] pipe tobacco, and snus.[ citation needed ]It is widely used because it is highly addictive and hard to discontinue using it. 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,
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.
Nicotine may not be harmless,but it is safer than inhaled tobacco smoke. As medicine, nicotine is used to help with quitting smoking and has good safety in this form. The accepted medical position in 2007 was that nicotine itself poses few health risks, except among certain vulnerable groups such as youth, but the ideal course of action for smokers is to quit all nicotine use.
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.
|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.|
|Buccal||Lozenge||Nausea, dyspepsia, flatulence, headache, upper respiratory tract infections, irritation (i.e., a burning sensation), hiccups, sore throat, coughing, dry lips, and oral mucosal ulceration.|
|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.|
|Intranasal||Nasal spray||Runny nose, nasopharyngeal and ocular irritation, watery eyes, sneezing, and coughing.|
|Oral inhalation||Inhaler||Dyspepsia, oropharyngeal irritation (e.g., coughing, irritation of the mouth and throat), rhinitis, and headache.|
|All (nonspecific)||Peripheral vasoconstriction, tachycardia (i.e., fast heart rate), elevated blood pressure, and increased alertness and cognitive performance.|
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.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.
A 2018 Cochrane review found that, in rare cases, nicotine replacement therapy can cause non-ischemic chest pain (i.e., chest pain that is unrelated to a myocardial infarction) and heart palpitations.The same review indicated that nicotine replacement therapy does not increase the incidence of serious cardiac adverse events (i.e., myocardial infarction, stroke, and cardiac death) relative to controls.
Although nicotine does not cause cancer in humans, as of 2012 [update] . A 2018 report by the National Academies of Sciences, Engineering, and Medicine concludes, “[w]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.”it is unclear whether it functions as a tumor promoter
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 (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. In cancer cells, nicotine promotes the epithelial–mesenchymal transition which makes the cancer cells more resistant to drugs that treat cancer.
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.
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.
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. 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 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
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). – which may occur within minutes – is believed to be due to respiratory paralysis.Respiratory stimulation (i.e., tachypnea) is one of the primary signs of nicotine poisoning. 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. Lethal nicotine poisoning rapidly produces seizures, and death
ΔFosB accumulation from excessive drug use
Nicotine is highly addictive.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. 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 (i.e., produces phosphorylated ΔFosB isoforms) in the nucleus accumbens when inhaled or injected frequently or at high doses, but not necessarily when ingested.Consequently, high daily exposure (possibly excluding oral route) to nicotine can cause ΔFosB overexpression in the nucleus accumbens, resulting in nicotine addiction.
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, 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.accidental ingestion of tobacco or tobacco products, or ingestion of nicotine-containing plants. 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. 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
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.
Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs),except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.
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 (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. – 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.This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the ventral tegmental area. Nicotine also appears to induce the release of endogenous opioids that activate opioid pathways in the reward system, since naltrexone
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 (and norepinephrine) into the bloodstream.
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.
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 (4.4%) 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 (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.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.
| NFPA 704 |
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. Nicotine is readily volatile (vapor pressure 5.5 ㎩ at 25 ℃) and dibasic (Kb1=1×10⁻⁶, Kb2=1×10⁻¹¹). On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (vitamin B3), and methylamine.
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. °C.The salts of (+)-nicotine are usually dextrorotatory. The hydrochloride and sulphate salts become optically inactive if heated in a closed vessel above 180
Anabasine is a structural isomer of nicotine, as both compounds have the molecular formula C 10 H 14 N 2.
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 (varying from 2–7 µg/kg, or 20–70 millionths of a percent wet weight ) in Solanaceaein plants from the family Solanaceae (such as potatoes, tomatoes, eggplant, and peppers ).
The amounts of nicotine of tomato varieties lowered substantially as the fruits ripened. 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.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 [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." The amount of nicotine eaten per day is roughly around 1.4 and 2.25
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.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.
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.
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. [ clarification needed ] and it was first synthesized by Amé Pictet and A. Rotschy in 1904.Its chemical empirical formula was described by Melsens in 1843, its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893,
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.
This section needs expansion. You can help by adding to it.(February 2019)
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. However, there is no minimum age requirement to use tobacco or nicotine products.
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.
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.
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.
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.
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.
Smoking cessation is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. Nicotine withdrawal makes the process of quitting often difficult.
Cotinine is an alkaloid found in tobacco and is also the predominant metabolite of nicotine. Cotinine is used as a biomarker for exposure to tobacco smoke. Cotinine is currently being studied as a treatment for depression, PTSD, schizophrenia, Alzheimer's disease and Parkinson's disease. Cotinine was developed as an antidepressant as a fumaric acid salt, cotinine fumarate, to be sold under the brand name Scotine but it was never marketed.
Nicotine replacement therapy (NRT) is a medically-approved way to take nicotine by means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting smoking by about 50% to 70%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of more than one type of NRT at a time may increase effectiveness.
Tobacco use has predominantly negative effects on human health and concern about health effects of tobacco has a long history. Research has focused primarily on cigarette tobacco smoking.
Cytisine, also known as baptitoxine and sophorine, is an alkaloid that occurs naturally in several plant genera, such as Laburnum and Cytisus of the family Fabaceae. It has been used medically to help with smoking cessation. Its molecular structure has some similarity to that of nicotine and it has similar pharmacological effects. Like varenicline, cytisine is a partial agonist of nicotinic acetylcholine receptors (nAChRs). Cytisine has a short half-life of 4.8 hours, and is rapidly eliminated from the body. The use of cytisine for smoking cessation remains relatively unknown outside Eastern Europe, however, it is currently being investigated in clinical trials in the United States, being conducted by Achieve Life Sciences.
Varenicline is a prescription medication used to treat nicotine addiction. It reduces both craving for and decreases the pleasurable effects of cigarettes and other tobacco products.
NicVAX is an experimental conjugate vaccine intended to reduce or eliminate physical dependence to nicotine. According to the U.S. National Institute of Drug Abuse, NicVAX can potentially be used to inoculate against nicotine addiction. This proprietary vaccine is being developed by Nabi Biopharmaceuticals of Rockville, MD. with the support from the U.S. National Institute on Drug Abuse. NicVAX consists of the hapten 3'-aminomethylnicotine which has been conjugated (attached) to Pseudomonas aeruginosa exoprotein A.
Nicotine withdrawal is a group of symptoms that occur in the first few weeks upon the abrupt discontinuation or decrease in intake of nicotine. Symptoms include intense cravings for nicotine, anger/irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger or weight gain, and difficulty concentrating. A smoking cessation program may improve one’s chance for success in quitting nicotine. Nicotine withdrawal is recognized in both the American Psychiatric Association Diagnostic and Statistical Manual and the WHO International Classification of Diseases.
Tobacco harm reduction (THR) is a public health strategy to lower the health risks to individuals and wider society associated with using tobacco products. It is an example of the concept of harm reduction, a strategy for dealing with the abuse of other drugs. Tobacco smoking is widely acknowledged as a leading cause of illness and death, and preventing smoking is vital to public health.
Lobeline is a pyridine alkaloid found in a variety of plants, particularly those in the genus Lobelia, including Indian tobacco, Devil's tobacco, cardinal flower, great lobelia, Lobelia chinensis, and Hippobroma longiflora. In its pure form, it is a white amorphous powder which is freely soluble in water.
An electronic cigarette or e-cigarette is a handheld electronic device that simulates the experience of smoking a cigarette. It works by heating a liquid which generates an aerosol, or "vapor", that is inhaled by the user. Using e-cigarettes is commonly referred to as vaping. The liquid in the e-cigarette, called e-liquid, or e-juice, is usually made of nicotine, propylene glycol, glycerine, and flavorings. Not all e-liquids contain nicotine.
Nicotine dependence is a state of dependence upon nicotine. Nicotine dependence is a chronic, relapsing disease defined as a compulsive craving to use the drug, despite harmful social consequences. Tolerance is another component of drug dependence. Nicotine dependence develops over time as a person continues to use nicotine. Nicotine dependence is a serious public health concern due to it being one of the leading causes of avoidable deaths worldwide.
Psychological dependence is a state that involves emotional–motivational withdrawal symptoms, e.g. anxiety and anhedonia, upon cessation of drug use or certain behaviours. It develops through frequent exposure to a psychoactive substance or behaviour, though behavioural dependence is less talked about. The specific mechanism involves a neuronal counter-adaption, which could be mediated through changes in neurotransmittor activity or altered receptor expression. Withdrawal symptoms can be attenuated by environmental enrichment and physical activity. Psychological dependence is not to be confused with physical dependence, which induces physical withdrawal symptoms upon discontinuation of use. However they are not mutually exclusive.
Studies across 20 countries show a strong association between schizophrenia and tobacco smoking, whereby people with schizophrenia are much more likely to smoke than those without the disease. For example, in the United States, 80% or more of people with schizophrenia smoke, compared to 20% of the general population in 2006.
The scientific community in United States and Europe are primarily concerned with the possible effect of electronic cigarette use on public health. There is concern among public health experts that e-cigarettes could renormalize smoking, weaken measures to control tobacco, and serve as a gateway for smoking among youth. The public health community is divided over whether to support e-cigarettes, because their safety and efficacy for quitting smoking is unclear. Many in the public health community acknowledge the potential for their quitting smoking and decreasing harm benefits, but there remains a concern over their long-term safety and potential for a new era of users to get addicted to nicotine and then tobacco. There is concern among tobacco control academics and advocates that prevalent universal vaping "will bring its own distinct but as yet unknown health risks in the same way tobacco smoking did, as a result of chronic exposure", among other things.
Jed Eugene Rose, Ph.D. is an American academic professor, inventor and researcher in the field of nicotine and smoking cessation. Rose is presently the President and CEO of the Rose Research Center, LLC in Raleigh, North Carolina. Additionally, he is the Director of the Duke Center for Smoking Cessation at Duke University Medical Center.
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.
Used as an aid to smoking cessation and for the relief of nicotine withdrawal symptoms.
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 ...
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
There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. ...
A meta-analysis of adverse events associated with NRT included 92 RCTs and 28 observational studies, and addressed a possible excess of chest pains and heart palpitations among users of NRT compared with placebo groups (Mills 2010). The authors report an OR of 2.06 (95% CI 1.51 to 2.82) across 12 studies. We replicated this data collection exercise and analysis where data were available (included and excluded) in this review, and detected a similar but slightly lower estimate, OR 1.88 (95% CI 1.37 to 2.57; 15 studies; 11,074 participants; OR rather than RR calculated for comparison; Analysis 6.1). Chest pains and heart palpitations were an extremely rare event, occurring at a rate of 2.5% in the NRT groups compared with 1.4% in the control groups in the 15 trials in which they were reported at all. A recent network meta-analysis of cardiovascular events associated with smoking cessation pharmacotherapies (Mills 2014), including 21 RCTs comparing NRT with placebo, found statistically significant evidence that the rate of cardiovascular events with NRT was higher (RR 2.29 95% CI 1.39 to 3.82). However, when only serious adverse cardiac events (myocardial infarction, stroke and cardiovascular death) were considered, the finding was not statistically significant (RR 1.95 95% CI 0.26 to 4.30).
Kis as follows; α2β4=9900nM , α3β2=14nM , α3β4=187nM , 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
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.
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
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.
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
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), ...
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).
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