Author: Alberto Umoret
Date: 27/05/2008



Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae), predominantly in tobacco and coca, and in lower quantities in tomato, potato, eggplant (aubergine), and green pepper.

Nicotine has been found to constitute approximately 0.6 - 3.0% of dry weight of tobacco, with biosynthesis taking place in the roots, and accumulating in the leaves. It functions as an antiherbivore chemical, being a potent neurotoxin with particular specificity to insects; therefore nicotine was widely used as an insecticide in the past, and currently nicotine derivatives 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 (effects of nicotine)
The pharmacological and behavioral characteristics that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.

Comparative study of two kinds of addictive behaviour; smoking and drug abuse.
Patterns of alcohol, cigarette, and caffeine and other drug use in two drug abusing populations.
Drug use and cigarette smoking in applicants for drug abuse treatment.
Cigarette smoking in alcohol and cocaine abusers.

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. Most of the nicotine is burned when a cigarette is smoked; however, enough is inhaled to provide the desired effects.


FDA classification


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, 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". 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). 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. Smoking also appears to interfere with development of Kaposi's sarcoma, breast cancer among women carrying the very high risk BRCA gene, preeclampsia, and atopic disorders such as allergic asthma. 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.


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.
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 (Cotinine is a byproduct of the metabolism 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).

Molecular mechanism

Nicotine acts on the nicotinic acetylcholine receptors, specifically

  • the ganglion type nicotinic receptor, that is present e.g. in the adrenal medulla
  • the CNS type nicotinic receptor. present in the CNS.

In small concentrations it increases the activity of these receptors.

  • By binding to ganglion type nicotinic receptors 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 adrenaline causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels
    In high doses, nicotine will cause a blocking of the nicotinic acetylcholine receptor, which is the reason for its toxicity and its effectiveness as an insecticide.
  • By binding to CNS type nicotinic receptors, nicotine increases dopamine levels in the reward circuits of the brain. In this way, it activates the reward system and generates feelings of pleasure. (binding to CNS)
    Furthermore, nicotine activates the sympathetic nervous system, 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.

Studies have shown that other ingredients in inhaled tobacco smoke (as opposed to pure nicotine) inhibit the production of monoamine oxidase (MAO), an enzyme responsible for breaking down monoaminergic neurotransmitters, such as dopamine, in the brain.

The involvement of AMP-activated protein kinases in the anti-inflammatory effect of nicotine in vivo and in vitro.
Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.
Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action.

secondo alcuni dati da me messi nei commenti sarebbe pro-infiammatoria ?????

With regard to neurological diseases, a large body of evidence suggests that the risks of Parkinson's disease or Alzheimer's disease might be twice as high for non-smokers than for smokers. Many such papers regarding Alzheimer's disease and Parkinson's Disease have been published.

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 also responsible for processing nicotine in the brain.

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

Neurochemical pathways involved in the protective effects of nicotine and ethanol in preventing the development of Parkinson's disease: Potential targets for the development of new therapeutic agents.
Nicotine and nicotinic receptors; relevance to Parkinson's disease.
Nicotinic receptors as CNS targets for Parkinson's disease.

A review of the effects of nicotine on schizophrenia.
Nicotine effects on brain function and functional connectivity in schizophrenia.

The therapeutic use of nicotine as a means of appetite-control and to promote weight loss is anecdotally supported by many ex-smokers who claim to put on weight after quitting. However studies of nicotine in mice suggests it may play a role in weight-loss that is independent of appetite. And studies involving the elderly suggest that nicotine affects not only weight loss, but also prevents some weight gain.

Side effects

Nicotine's major side effect is dependence

Mechanisms of Nicotine Dependence.
Hooked from the first cigarette.
Cigarette smoking and nicotine addiction.
Neural mechanisms underlying nicotine dependence.

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.

The endogenous cannabinoid system modulates nicotine reward and dependence.

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. 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 (namely cocaine and heroin, which reduce reward pathway sensitivity). 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 ethanol or heroin withdrawal. 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.

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

Pharmacotherapy for nicotine dependence.
New medications for nicotine dependence treatment.
Nicotine replacement therapy for smoking cessation.


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. This designates nicotine an extremely deadly poison. It is more toxic than many other alkaloids such as cocaine, which has an LD50 of 95.1 mg/kg when administered to mice. Spilling liquid nicotine on human skin could result in death.

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 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 create a more favourable environment for cancer to develop. Thus nicotine plays an indirect role in carcinogenesis. (nicotine effects on cells)

Multiple roles of nicotine on cell proliferation and inhibition of apoptosis: Implications on lung carcinogenesis.
Nicotine, lung and cancer.

At least one study has concluded that exposure to nicotine alone, not simply as a component of cigarette smoke, could be responsible for some of the neuropathological changes observed in infants dying from Sudden Infant Death Syndrome (SIDS).

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. However, research on nicotine as administered through a patch or gum is ongoing.

Link to circulatory disease (mi sembrano dubbie queste affermazioni: la nicotina mima acetilcolina e quindi dovrei avere vasodilatazione)

Nicotine has very powerful effects on arteries throughout the body. Nicotine is a stimulant, speeding up the heart by about 20 beats per minute with every cigarette; 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.

Nicotine increases the risk of blood clots significantly. 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, arteries going to the extremities, are also highly susceptible to the vasoconstrictor effects of nicotine as well as the increased risk of clots and clogging.

2008-07-08T13:35:41 - Gianpiero Pescarmona

Ridurre ciò che è già scritto sulla wikipedia

Acute Effect of Cigarette Smoke and Nicotine on Airway Blood Flow and Airflow in Healthy Smokers 2006

Kanwaldeep Randhawa1, 2 Contact Information, Eliana Mendes2 and Adam Wanner2 2006

Abstract Cigarette smoke contains irritants and vasoactive substances. We wanted to determine the effect of smoking a cigarette and of nasally or orally inhaled nicotine on airway blood flow (Qaw) and airflow in smokers. In ten healthy current smokers, Qaw, FEV1, and FEF25–75 were measured before and at 5, 30, and 180 min after smoking a cigarette. The effects of systemic nicotine using a nicotine nasal spray and local nicotine using a nicotine inhaler were also studied. Mean (± SE) Qaw increased by 81% ± 16% (p = 0.03) 5 min after smoking a cigarette and was no longer different from baseline at 30 and 180 min. Nicotine nasal spray and nicotine oral inhaler had no effect on Qaw. FEV1 and FEF25-75 remained unchanged after smoking a cigarette and after local or systemic nicotine administration. Smoking a cigarette is followed by a transient increase in airway blood flow but no changes in airflow. Nicotine, at the rate and dose provided by the nasal spray (systemic action) and oral inhaler (local and systemic action), does not appear to be involved in the Qaw change, suggesting a pharmacologic or nonspecific irritant effect of other cigarette smoke constituents.

NF-kB activation by Nicotine

Progress of the study of rho-kinase and future perspective of the inhibitor. 2007

Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels. 2004

Effect on adrenals

From W: By binding to ganglion type nicotinic receptors the adrenal medulla nicotine increases flow of adrenaline (epinephrine),

AddThis Social Bookmark Button