Nicotine
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Nicotine
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| Systematic (IUPAC) name | |
| 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine | |
| Chemical data | |
| Formula | C10H14N2 |
| Mol. mass | 162.26 g/mol |
| Physical data | |
| Density | 1.01 g/cm³ |
| Melt. point | -79 °C (-110 °F) |
| Boiling point | 247 °C (477 °F) |
Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) which constitutes approximately 0.6-3.0% of dry weight of tobacco,[1][2] 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, 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 one of the main factors responsible for the dependence-forming properties of tobacco smoking. According to the American Heart Association, "Nicotine addiction has historically been one of the hardest addictions to break." The pharmacological and behavioral characteristics that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.[3]
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History and name
Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after Jean Nicot de Villemain, French ambassador in Portugal, who sent tobacco and seeds from Brazil to Paris in 1560 and promoted their medicinal use. Nicotine was first isolated from the tobacco plant in 1828 by German chemists Posselt & Reimann.[citation needed] Its chemical empirical formula was described by Melsens in 1843,[4] its structure was discovered by Adolf Pinner in 1893, and it was first synthesized by A. Pictet and Crepieux in 1904.[citation needed]
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.
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.[5] The salts of the (+)-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. The half life of nicotine in the body is around two hours.[6] The amount of nicotine inhaled with tobacco smoke is a fraction of the amount contained in the tobacco leaves. 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 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.
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 the increased levels of dopamine in the reward circuits of the brain is what is responsible for the euphoria and relaxation and eventual addiction caused by nicotine consumption.
Tobacco smoke contains the monoamine oxidase inhibitors harman and norharman[7], and significantly decreases MAO activity in smokers.[7][8] 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[9][10] .
In PNS
Nicotine also activates the sympathetic nervous system,[12] 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.
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[13]
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 smoke.[citation needed]
