Nicotine

Nicotine is an organic compound, a pyrrolidine-like alkaloid found naturally in the nightshade family of plants, such as tobacco and tomatoes. It constitutes 0.3 to 5% of the tobacco plant by dry weight, with biosynthesis taking place in the roots, and accumulates in the leaves. It is a potent nerve poison and is included in many insecticides. In lower concentrations, the substance is a stimulant and is one of the main factors leading to the habit-forming qualities of tobacco smoking. Nicotine seems to provide both a stimulant and a depressant effect, and it is likely that the effect it has at any time is determined by the mood of the user, the environment and the circumstances of use. Studies have suggested that low doses have a depressant effect, whilst higher doses have stimulant effect. Nicotine has limited carcinogenic effects, inhibiting the body's ability to destroy potentially cancerous cells. However, nicotine does not promote the development of cancer in healthy cells. In addition to the tobacco plant, nicotine is also found in lower quantities in other members of the Solanaceae (nightshade) family, which includes tomato, potato, eggplant (aubergine), and green pepper. Nicotine alkaloids are also found in the leaves of the coca plant.

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 95 °C in air despite a low vapor pressure. Because of this, most nicotine is burned when a cigarette is smoked; however, enough is inhaled to cause the body to form a powerful addiction.

Effects on the body
In small doses nicotine has a stimulating effect, increasing activity, alertness and memory. Repeat users report a pleasant relaxing effect. It also increases the heart rate and blood pressure and reduces the appetite. In large doses it may cause vomiting and nausea. The LD50 of nicotine (that is, the lethal dosage reported to kill 50% of the population) is 50 mg/kg for rats and 3 mg/kg for mice. 40–60 mg can be a lethal dosage for adult human beings. This dose makes it an extremely deadly poision. It is more toxic than many other alkaloids such as cocaine, which has a lethal dose of 1000mg.

Repeat users of nicotine very often develop a physical dependency to the chemical. A report released on May 16, 1988, by United States Surgeon General C. Everett Koop stated that the addictive properties of nicotine are similar to those of heroin and cocaine; although many people do not agree with such a comparison.

Physical withdrawal symptoms include irritability, headaches, anxiety, cognitive disturbances and sleep disruption. These symptoms peak at around 48–72 hours and generally cease after two to six weeks.

Although the amount of nicotine inhaled with tobacco smoke is quite small (most of the substance is destroyed by the heat), it is still sufficient to cause dependence. 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, often called Dip, Snuff, or snus, which is held in the mouth between the lip and gum, the amount released into the body tends to be much greater than smoked tobacco.

As nicotine enters the body, it quickly gets distributed through the bloodstream and can cross the blood-brain barrier. On average it takes about seven seconds for the substance to reach the brain. It acts on the nicotinic acetylcholine receptors. In small concentrations it increases the activity of these receptors, among other things leading to an increased flow of adrenaline, a stimulating hormone. The release of adrenaline causes an increase in heart rate, blood pressure and respiration, as well as higher glucose levels in the blood. Cotinine is a break-down product of nicotine which remains in the blood for up to 48 hours and can be used as an indicator of a person's exposure to smoke. In high doses, nicotine will cause a depolarizing block of the nicotinic acetylcholine receptor, which is the reason for its toxicity and its effectiveness as an insecticide.

In addition, nicotine increases dopamine levels in the reward circuits of the brain. Studies have shown that smoking tobacco inhibits monoamine oxidase (MAO), an enzyme responsible for breaking down monoaminergic neurotransmitters such as dopamine, in the brain. It is currently believed that nicotine by itself does not inhibit the production of monoamine oxidase (MAO), but that other ingredients in inhaled tobacco smoke are believed to be responsible for this activity. In this way, it generates feelings of pleasure. This reaction is similar to that caused by cocaine and heroin and is another reason people keep smoking: to sustain high dopamine levels.

It has been noted that the majority of people diagnosed with schizophrenia smoke tobacco. Estimates for the number of schizophrenics that 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.  More recent research has found the reverse, that it is a risk factor without long-term benefit, used only for its short term effects. 

Nicotine and its metabolites are being researched for the treatment of a number of disorders, including ADHD, Parkinson's Disease and Alzheimer's Disease.

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. Its teratogenic properties 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. However, nicotine and the increased acetylcholinic 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 creates a more favourable environment for cancer to develop. Thus nicotine plays an indirect role in carcinogenesis. It is also important to note that its addictive properties are often the primary motivating factor for tobacco smoking, contributing to the proliferation of cancer.

Therapeutic uses
The primary therapeutic use of nicotine is in treating nicotine dependence. Controlled levels of nicotine are given to a patient through gums, dermal patches, or nasal sprays in an effort to wean them off of their dependence.

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

History and name
Nicotine is named after the tobacco plant Nicotiana tabacum which in turn is named after Jean Nicot, who sent tobacco seeds from Portugal to Paris in 1550 and promoted its medicinal use. It was first isolated in 1828 by German chemists Posselt & Reimann; its empirical formula C10H14N2 was established in 1843 by Melsens; its molecular structure (3-(1-methyl-2-pyrrolidinyl)pyridine) was established in 1893 by Adolf Pinner, and it was first synthesized by A. Pictet and Crepieux in 1904.