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== History and name ==
== History and name ==
it in fags and its makes u have a boost of energy like caffeine
Nicotine is named after the tobacco plant ''[[Nicotiana tabacum]]'' which in turn is named after [[Jean Nicot|Jean Nicot de Villemain]], [[France|French]] ambassador in [[Portugal]], who sent tobacco and seeds from [[Brazil]] to [[Paris]] in 1560 and promoted their medicinal use. Nicotine was first isolated from the tobacco plant in 1828 by [[Germany|German]] chemists Posselt & Reimann, who considered it a poison.<!--Fight be in: Magazin der Pharmacie 24. 138. 1828--><ref>{{cite journal

| title = "Nicotine psychopharmacology", research contributions to United States and global tobacco regulation: A look back and a look forward
it LUSh
| journal = Psychopharmacology

| volume = 184
KEEP SMOKING EVERY ONE :)
| issue = 3-4

| pages = 286–291

| year = 2006

| url = http://www.springerlink.com/content/75462q6mq88g4575/fulltext.pdf

| doi = 10.1007/s00213-006-0308-4
SMOKING IS LUSH TRY IT NOW KIDS
| pmid = 16463054

| last1 = Henningfield
KIDS GO ASK YOUR MUM FOR FAG AND TRY IT YOU WILL LOVE IT
| first1 = JE
| last2 = Zeller
| first2 = M
| author1 = Henningfield, Jack E
| author2 = Zeller, Mitch}}</ref> Its chemical [[empirical formula]] was described by Melsens in 1843,<ref>{{cite journal
| title = Über das Nicotin
| author = Melsens
| journal = [[Journal für Praktische Chemie]]
| volume = 32
| issue = 1
| pages = 372–377
| year = 1844
| url =
| doi = 10.1002/prac.18440320155}}</ref> its structure was
discovered by Garry Pinner in 1893, and it was first synthesized by A. Pictet and Crepieux in 1904.<ref>http://medicolegal.tripod.com/toxicchemicals.htm Comptes rendus, 1903, 137, p 860</ref>


== Chemistry ==
== Chemistry ==

Revision as of 12:23, 15 April 2010

This article is about the chemical compound. For other uses, see Nicotine (disambiguation).
Nicotine
Clinical data
Dependence
liability		Medium to high
Routes of
administration		smoked (as smoking tobacco, mapacho, etc.), insufflated (as tobacco snuff or nicotine nasal spray), chewed (as nicotine gum, tobacco gum or chewing tobacco), transdermal (as nicotine patch, nicogel or topical tobacco paste), intrabuccal (as dipping tobacco, snuffs, dissolvable tobacco or creamy snuff), intravenously (as NicVAX)[clarification needed], vaporized (as electronic cigarette, etc.), directly inhaled (as nicotine inhaler), oral (as nicotini)
ATC code
Legal status
Legal status
  • AU: Unscheduled
  • UK: Unscheduled
  • US: WARNING[1]Unscheduled, but age restricted.
Pharmacokinetic data
Bioavailability20 to 45% (oral)
Metabolismhepatic
Elimination half-life2 hours
Identifiers
  • 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.000.177 Edit this at Wikidata
Chemical and physical data
FormulaC10H14N2
Molar mass162.26 g/mol g·mol−1
3D model (JSmol)
Density1.01 g/cm3
Melting point−79 °C (−110 °F)
Boiling point247 °C (477 °F)
  • C1=CC=NC=C1[C@@H]2CCCN2C
  (verify)

Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) which constitutes approximately 0.6–3.0% of dry weight of tobacco,[2][3] with biosynthesis taking place in the roots, and accumulating in the leaves. It functions as an antiherbivore chemical with particular specificity to insects; therefore nicotine was widely used as an insecticide in the past,[4][5] and currently nicotine analogs such as imidacloprid continue to be widely used.

In low concentrations (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals and is the main factor responsible for the dependence-forming properties of tobacco smoking. According to the American Heart Association, the "nicotine addiction has historically been one of the hardest addictions to break." The pharmacological and behavioral characteristics that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.[6] Nicotine content in cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.6% per year between the years of 1998 and 2005. This was found for all major market categories of cigarettes.[7]

History and name

it in fags and its makes u have a boost of energy like caffeine

it LUSh

KEEP SMOKING EVERY ONE :)



SMOKING IS LUSH TRY IT NOW KIDS

KIDS GO ASK YOUR MUM FOR FAG AND TRY IT YOU WILL LOVE IT

Chemistry

Nicotine is a hygroscopic, oily liquid that is miscible with water in its base form. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water soluble. Nicotine easily penetrates the skin. As shown by the physical data, free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at 308 K (35 °C; 95 °F) in air despite a low vapor pressure. Because of this, most of the nicotine is burned when a cigarette is smoked; however, enough is inhaled to provide the desired effects. The amount of nicotine inhaled with tobacco smoke is a fraction of the amount contained in the tobacco leaves.[citation needed]

Optical activity

Nicotine is optically active, having two enantiomeric forms. The naturally-occurring form of nicotine is levorotatory, with [α]D = –166.4°. The dextrorotatory form, (+)-nicotine, has only one-half the physiological activity of (–)-nicotine. It is therefore weaker in the sense that a higher dose is required to attain the same effects.[8] The salts of (+)-nicotine are usually dextrorotatory.

Pharmacology

Pharmacokinetics

As nicotine enters the body, it is distributed quickly through the bloodstream and can cross the blood-brain barrier. On average it takes about seven seconds for the substance to reach the brain when inhaled.[citation needed] The half life of nicotine in the body is around two hours.[9]

The amount of nicotine absorbed by the body from smoking depends on many factors, including the type of tobacco, whether the smoke is inhaled, and whether a filter is used. For chewing tobacco, dipping tobacco, snus and snuff, which are held in the mouth between the lip and gum, or taken in the nose, the amount released into the body tends to be much greater than smoked tobacco. Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6). A major metabolite is cotinine.

Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.[10]

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.[11]

Pharmacodynamics

Nicotine acts on the nicotinic acetylcholine receptors, specifically the ganglion type nicotinic receptor and one CNS nicotinic receptor. The former is present in the adrenal medulla and elsewhere, while the latter is present in the central nervous system (CNS). In small concentrations, nicotine increases the activity of these receptors. Nicotine also has effects on a variety of other neurotransmitters through less direct mechanisms.

In CNS

By binding to nicotinic acetylcholine receptors, nicotine increases the levels of several neurotransmitters - acting as a sort of "volume control". It is thought that increased levels of dopamine in the reward circuits of the brain are responsible for the euphoria and relaxation and eventual addiction caused by nicotine consumption. Nicotine has a higher affinity for acetylcholine receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis.[12] Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.[13]

Tobacco smoke contains the monoamine oxidase inhibitors harman, norharman,[14] anabasine, anatabine, and nornicotine. These compounds significantly decrease MAO activity in smokers.[14][15] MAO enzymes break down monoaminergic neurotransmitters such as dopamine, norepinephrine, and serotonin.

Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem regions[16][17] but not habenulopeduncular structures.[18] Alpha4beta2 and alpha6beta2 receptors, present in the ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.[19]

In SNS

Nicotine also activates the sympathetic nervous system,[20] acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream. Nicotine also has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or its irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals.[21]

In adrenal medulla

By binding to ganglion type nicotinic receptors in the adrenal medulla nicotine increases flow of adrenaline (epinephrine), a stimulating hormone. 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.[22]

Side effects of nicotine.[23]

Cotinine is a byproduct of the metabolism of nicotine which remains in the blood for up to 48 hours. It can therefore be used as an indicator of a person's exposure to nicotine.[citation needed]

Psychoactive effects

Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.[24] First causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness.[25] By reducing the appetite and raising the metabolism, some smokers may lose weight as a consequence.[26][27]

When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and immediately stimulates the release of many chemical messengers including acetylcholine, norepinephrine, epinephrine, vasopressin, arginine, dopamine, autocrine agents, and beta-endorphin.[28] This release of neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance concentration[29] and memory due to the increase of acetylcholine. It also appears to enhance alertness due to the increases of acetylcholine and norepinephrine. Arousal is increased by the increase of norepinephrine. Pain is reduced by the increases of acetylcholine and beta-endorphin. Anxiety is reduced by the increase of beta-endorphin. Nicotine also extends the duration of positive effects of dopamine[30] and increases sensitivity in brain reward systems.[31] Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.[32]

Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine.[33] This stimulates nerve transmission. When they wish to relax, they take deep puffs, which produce a high level of blood nicotine, which depresses the passage of nerve impulses, producing a mild sedative effect. At low doses, nicotine potently enhances the actions of norepinephrine and dopamine in the brain, causing a drug effect typical of those of psychostimulants. At higher doses, nicotine enhances the effect of serotonin and opiate activity, producing a calming, pain-killing effect. Nicotine is unique in comparison to most drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use. (Another drug that behaves similarly is ethanol.)

Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties.[34] However, only after coadministration with an MAOI, such as those found in tobacco, nicotine produces significant behavioral sensitization, a measure of addiction potential. This is similar in effect to amphetamine.[35]

A 21 mg patch applied to the left arm

Nicotine gum, usually in 2-mg or 4-mg doses, and nicotine patches are available, as well as smokeless tobacco which do not have all the other ingredients in smoked tobacco.

Dependence and withdrawal

See also: Smoking cessation

Modern research shows that nicotine acts on the brain to produce a number of effects. Specifically, its addictive nature has been found to show that nicotine activates reward pathways—the circuitry within the brain that regulates feelings of pleasure and euphoria.[36]

Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin, though chronic treatment has an opposite effect on reward thresholds.[citation needed] Like other physically addictive drugs, nicotine causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. In addition, the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. The net effect is an increase in reward pathway sensitivity, opposite of other drugs of abuse such as cocaine and heroin, which reduce reward pathway sensitivity.[31] This neuronal brain alteration persists for months after administration ceases. Due to an increase in reward pathway sensitivity, nicotine withdrawal is relatively mild compared to alcohol or heroin withdrawal.[citation needed] Nicotine also has the potential to cause dependence in many animals other than humans. Mice have been administered nicotine and exhibit withdrawal reactions when its administration is stopped.[citation needed]

A study found that nicotine exposure in adolescent mice retards the growth of the dopamine system, thus increasing the risk of substance abuse during adolescence.[37]

Immunology prevention

Because of the severe addictions and the harmful effects of smoking, vaccination protocols have been developed. The principle is under the premises that if an antibody is attached to a nicotine molecule, it will be prevented from diffusing through the capillaries, thus making it less likely that it ever effects the brain by binding to nicotinic acetylcholine receptors.

These include attaching the nicotine molecule to a hapten such as Keyhole limpet hemocyanin or a safe modified bacterial toxin to elicit an active immune response. Often it is added with bovine serum albumin.

Additionally, because of concerns with the unique immune systems of individuals being liable to produce antibodies against endogenous hormones and over the counter drugs, monoclonal antibodies have been developed for short term passive immune protection. They have half-lives varying from hours to weeks. Their half-lives depend on their ability to resist degradation from pinocytosis by epithelial cells.[38]

Toxicology

See also: Nicotine poisoning

The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 40–60 mg (0.5-1.0 mg/kg) can be a lethal dosage for adult humans.[39][40] Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine, which has an LD50 of 95.1 mg/kg when administered to mice. It is impossible however to overdose on nicotine through smoking alone (though a person can overdose on nicotine through a combination of nicotine patches, nicotine gum, and/or tobacco smoking at the same time).[41][42] Spilling an extremely high concentration of nicotine onto the skin can result in intoxication or even death since nicotine readily passes into the bloodstream from dermal contact.[43]

The carcinogenic properties of nicotine in standalone form, separate from tobacco smoke, have not been evaluated by the IARC, and it has not been assigned to an official carcinogen group. The currently available literature indicates that nicotine, on its own, does not promote the development of cancer in healthy tissue and has no mutagenic properties. However, nicotine and the increased cholinergic activity it causes have been shown to impede apoptosis, which is one of the methods by which the body destroys unwanted cells (programmed cell death). Since apoptosis helps to remove mutated or damaged cells that may eventually become cancerous, the inhibitory actions of nicotine may create a more favourable environment for cancer to develop, though this also remains to be proven.[44]

The teratogenic properties of nicotine have not yet been adequately researched, and while the likelihood of birth defects caused by nicotine is believed to be very small or nonexistent, nicotine replacement product manufacturers recommend consultation with a physician before using a nicotine patch or nicotine gum while pregnant or nursing.[44][unreliable source?]

Women who use nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth defects, says a study that looked at about 77,000 pregnant women in Denmark. The study found that women who use nicotine-replacement therapy in the first 12 weeks of pregnancy have a 60 percent greater risk of having babies with birth defects, compared to women who are non-smokers, the Daily Mail reported. The findings were published in the journal Obstetrics and Gynaecology.

Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency added nicotine to the list of chemicals known to the state to cause developmental toxicity, for the purposes of Proposition 65.[45]

Nicotine and oxidative stress

Nicotine is detoxified by the cytochrome p450 in the liver.[10]

Link to circulatory disease

Nicotine has very powerful effects on arteries throughout the body. Nicotine is a stimulant, it raises blood pressure, and is a vasoconstrictor, making it harder for the heart to pump through the constricted arteries. It causes the body to release its stores of fat and cholesterol into the blood.[citation needed]

It has been speculated[who?] that nicotine increases the risk of blood clots by increasing plasminogen activator inhibitor-1, though this has not been proven. Plasma fibrinogen levels are elevated in smokers and are further elevated during acute COPD exacerbation. Also Factor XIII, which stabilizes fibrin clots, is increased in smokers. But neither of these two effects has been shown to be caused by nicotine [1] as of 2009. If blood clots in an artery, blood flow is reduced or halted, and tissue loses its source of oxygen and nutrients and dies in minutes.

Peripheral circulation in arteries going to the extremities is also highly susceptible to the vasoconstrictor effects of nicotine and the increased risk of clots and clogging.[citation needed]

Therapeutic uses

The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with its risks to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence.

However, in a few situations, smoking has been observed to apparently be of therapeutic value to patients. These are often referred to as "Smoker’s Paradoxes".[46] Although in most cases the actual mechanism is understood only poorly or not at all, it is generally believed that the principal beneficial action is due to the nicotine administered, and that administration of nicotine without smoking may be as beneficial as smoking, without the higher risk to health due to tar and other ingredients found in tobacco.

For instance, recent studies suggest that smokers require less frequent repeated revascularization after percutaneous coronary intervention (PCI).[46] Risk of ulcerative colitis has been frequently shown to be reduced by smokers on a dose-dependent basis; the effect is eliminated if the individual stops smoking.[47][48] Smoking also appears to interfere with development of Kaposi's sarcoma,[49] breast cancer among women carrying the very high risk BRCA gene,[50] preeclampsia,[51] and atopic disorders such as allergic asthma.[52] A plausible mechanism of action in these cases may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects.[53]

Tobacco smoke has been shown to contain compounds capable of inhibiting MAO. Monoamine oxidase is responsible for the degradation of dopamine in the human brain. When dopamine is broken down by MAO-B, neurotoxic by-products are formed, possibly contributing to Parkinson's and Alzheimers disease.[54] Many such papers regarding Alzheimer's disease[55] and Parkinson's Disease[56] have been published. Recent studies find no beneficial link between smoking and Alzheimer's disease and in some cases, suggest it may actually result in an earlier onset of the disease.[57][58][59][60] However, nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans.[61][62][63]

Recent studies have indicated that nicotine can be used to help adults suffering from autosomal dominant nocturnal frontal lobe epilepsy. The same areas that cause seizures in that form of epilepsy are responsible for processing nicotine in the brain.[64]

It has been noted that the majority of people diagnosed with schizophrenia smoke tobacco[citation needed]. Estimates for the proportion of schizophrenics who smoke range from 75% to 90%. It was recently argued that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine.[65][66] More recent research has found that mildly-dependent users got some benefit from nicotine, but not those who were highly-dependent.[67] All of these studies are based only on observation, and no interventional (randomized) studies have been done. Research on nicotine as administered through a patch or gum is ongoing.

Nicotine improves ADHD symptoms and appears to have effects in the brain that are similar to those of stimulants. Although such findings should certainly not encourage anyone to smoke, some studies are focusing on benefits of nicotine therapy in adults with ADHD.[68]

Research as a potential basis for an antipsychotic agent

However, when the metabolites of nicotine were isolated and their effect on first the animal brain and then the human brain in people with schizophrenia were studied, it was shown that the effects helped with cognitive and negative symptoms of schizophrenia. Therefore, the nicotinergic agents, as antipsychotics which do not contain nicotine but act on the same receptors in the brain are showing promise as adjunct antipsychotics in early stages of FDA studies on schizophrenia. The prepulse inhibition (PPI) is a phenomenon in which a weak prepulse attenuates the response to a subsequent startling stimulus. Therefore, PPI is believed to have face, construct, and predictive validity for the PPI disruption in schizophrenia, and it is widely used as a model to study the neurobiology of this disorder and for screening antipsychotics.[69] Additionally, studies have shown that there are genes predisposing people with schizophrenia to nicotine use.[70]

Therefore with these factors taken together the heavy usage of cigarettes and other nicotine related products among people with schizophrenia may be explained and novel antipsychotic agents developed that have these effects in a manner that is not harmful and controlled and is a promising arena of research for schizophrenia.

See also

References

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