Nicotine

Nicotine is an organic compound, an alkaloid found mainly in the tobacco plant (Nicotiana tabacum), with a high concentration in its leaves (it constitutes about 5% of the weight of the plant and between 0.6% and 3% of the weight of dry tobacco) and also being present in other plants of the Solanaceae family, although marginally (in the range of 2–7 µg/kg), as in the case of tomato, eggplant, pepper and potato. In even more marginal quantities, it has been found in other plants such as cauliflower, green pepper or black tea. It is synthesized in areas of greater activity of the roots of tobacco plants and is transported by the sap to the green leaves. The deposit is made in the form of salts of organic acids.

It is a potent poison and has even been used historically as an insecticide. In low concentrations, the substance is a stimulant and is one of the main factors in tobacco addiction. It is polar and soluble in water.

History

Nicotine was named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador to Portugal, Jean Nicot de Villemain, who sent the tobacco and seeds to Paris in 1560, presented it to the King of France, and promoted its medicinal use. The tobacco and its seeds reached Ambassador Nicot from Brazil, sent by Luis de Gois, a Portuguese settler from São Paulo. Smoking was believed to protect against disease, particularly the plague. By the late 17th century, it was not only smoked but also used as an insecticide.

After World War II, more than 2,500 tons of nicotine insecticide was used worldwide, although as early as the 1980s nicotine insecticide use had fallen below 200 tons. This was due to the availability of other cheaper insecticides that were less harmful to mammals.

Currently, nicotine, even in the form of tobacco dust, is prohibited as a pesticide for organic farming in the United States. In 2008, the EPA received a request to deregister the last nicotine-containing pesticide registered in the United States and as of January 1, 2014 this pesticide is no longer available for sale.

Nicotine was isolated from the tobacco plant in 1828 by the German physician Wilhelm Heinrich Posselt and his compatriot, the chemist Karl Ludwig Reimann, who considered it a poison. Its empirical chemical formula was described by Louis Melsens in 1843, and its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and first synthesized by Amé Pictet and A. Rotschy in 1904.

Nicotine addiction

Cigarette smoking is the predominant form of nicotine addiction worldwide. In addition, sales and consumption of smokeless tobacco products have increased substantially. Nicotine is one of the most addictive psychoactive substances that exist.

Most cigarettes on the world market today contain between 10 and 20 milligrams (mg) or more of nicotine. By inhaling the smoke, the average smoker ingests between 1 and 2 mg of nicotine per cigarette. The molecule reaches the smoker's brain quickly. When inhaled, the smoke delivers the nicotine to the lungs along with the associated tar particles; from there, it passes into the blood through the alveoli. Ten to sixty seconds later, nicotine crosses the blood-brain barrier and enters the brain.

When smoke is not inhaled, nicotine is absorbed more slowly through the mucous membranes of the mouth. The same happens when tobacco is taken orally ("chewing" tobacco) or nasally (snuff).

Of the approximately 4,000 substances contained in cigarettes, only nicotine creates dependency. Its effect is disastrous in the ventral segment of the midbrain and in the nucleus accumbens of the forebrain, in areas that are part of the reward system. Nicotine, an analogue of the neurotransmitter acetylcholine, here binds to the nicotinic cholinergic receptors (nAChR) of neurons, thus causing them to release abundant dopamine.

The cause of nicotine creating addiction is that, although initially the GABAergic neurons to which it couples release the neurotransmitter gamma-aminobutyric acid (GABA) that stimulates the release of dopamine in neighboring neurons, if they are overexcited by nicotine, dopamine secretion is limited.

The long-term consequence of this is that cells adapt their biochemistry. This occurs in two phases: first, the number of nicotine receptors increases, thereby increasing dopamine secretion; however, over time neurons react less immediately and equally to nicotine, so the need to ingest larger amounts increases.

Therapies

There are basically three therapeutic lines in the fight against nicotine addiction: pharmacological, alternative nicotine therapy to smoking; and cognitive-behavioral psychological therapy. In all cases, it is considered that the coadjuvant of the psychological predisposition is essential to be able to overcome the addiction.

Pharmacological therapy is carried out with the use of drugs that imitate the nicotine molecule and that replace it in the fixation in the nerve receptors; the active substance bupropion is the most widely used, in addition to varenicline and cytisine (marketed as "Tabex"), nicotinic agonists that are consumed in pill form. The antiepileptic topiramate, which inhibits the transmission of excitatory neurotransmitters by acting on the kainate receptor, has also been used. All of these medications also produce corresponding side effects.

The therapy of administering nicotine in limited doses through alternative means (gum, patches, pills and inhalers) presents the problem of its contraindication for those with problems precisely derived from the consumption of nicotine through tobacco and, even, the possibility that she herself creates an addiction. But if used for short periods of no more than 9 weeks, smoked nicotine substitutes can help addicted smokers who quit smoking to overcome withdrawal. Patches are used daily with a constant concentration of nicotine for 3 weeks and then they are changed to others with a lower nicotine dose. Meanwhile, the brain learns to function without nicotine and acquires other healthy habits. The fact that the patches release nicotine constantly does not generate addiction because there is no peak of nicotine in the blood, which is what reinforces the desire to smoke (it is what the smoker enjoys when lighting a cigarette). Properly used nicotine substitutes, along with other smoking cessation strategies, can be very effective and safe.

Cognitive behavioral therapy has been shown to be an effective approach to smoking cessation. It can be used alone, which has the advantage of not presenting any pharmacological risk, or combined with the previous approaches. Also the use of psilocybin in the context of a cognitive behavioral therapy treatment has been studied.

Chemical identification

Nicotine was first isolated from the tobacco plant in 1828 by Wilhelm Heinrich Posselt and Karl Ludwig Reimann in Germany, who considered it a poison. Its chemical composition was first described by Louis Melsens in 1843, and its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893.

Pharmacodynamics

Nicotine selectively binds to acetylcholine receptors in autonomic ganglia, the adrenal cortex, and the brain. It causes in the central nervous system a stimulating effect on vigilance, alertness and cognitive performance (low doses), and a reinforcing or rewarding effect on the limbic system, mediated by the neural pathway of pleasure (high doses). Intravenous administration activates neurohormonal systems, with release of acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta endorphin, growth hormone and ACTH. Cardiovascular effects of nicotine include peripheral vasoconstriction, tachycardia, and hypertension.

Nicotine metabolism

Nicotine is metabolized in the liver by means of the cytochrome P450 (CIP) group of enzymes (enzymes that have the function of eliminating substances that are not synthesized by the body itself), and it is converted into cotinine to be eliminated by the body. urine. In humans, 70 to 80% of nicotine is metabolized by CYP2A6, of which three variants have been identified: the normal CYP2A6*1, and two others associated with reduced activity of the enzyme. The presence of abnormal variants among smokers is less frequent than among non-smokers. Those with abnormal variants smoke fewer cigarettes per day and are more successful in quitting.

There are at least 3 other metabolites of nicotine in addition to nicotinine, nornicotine, and aminoketones. On these, some studies of the concentrations in blood and in the central nervous system have been made. It has been seen that nicotine tends to accumulate, just like nornicotine.