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Nicotine

Nicotine is a tobacco alkaloid which is present in smoke. It stimulates the nicotinic receptors present in autonomic ganglia and brain. It is used as a drug and insecticide.

Action on the autonomic nervous system: ganglionic effect

Nicotine, initially and in low doses, stimulates the ganglionic receptors of the autonomic nervous system, which results in acetylcholine release by the cholinergic terminations, and of noradrenaline release by adrenergic terminations and adrenal medulla. It is only in very high doses that it inhibits ganglionic transmission.

Cardiovascular action

The analysis of cardiovascular modifications produced by nicotine in an anesthetized animal accounts for the complexity of its effects. An intravenous injection of nicotine in moderate dose elicits successively:

  1. hypotension by stimulation of the parasympathetic ganglion and release of acetylcholine which slows the heart and decreases the force of its contractions. This hypotension is prevented by atropine.
  2. hypertension by stimulation of the sympathetic ganglions inducing catecholamine release and cardiac stimulation and vasoconstriction. This hypertension is inhibited by adrenergic alpha-1 blocking agents.

The selective antagonist of the stimulation of the autonomic nervous system by nicotine is a ganglioplegic agent such as penthonium which blocks the nicotinic receptors of ganglia.

Repetitive administration of nicotine leads to a progressive attenuation of its effects, this is an example of tachyphylaxis; the parasympathetic effect, i.e. hypotension attenuates and disappears before the sympathetic component, i.e. hypertension.

It is only with extremely high doses that a paralysis of sympathetic ganglia is obtained resulting in a lowering of arterial pressure.

Action on smooth muscle and secretions

Nicotine causes nausea, vomiting, as can be observed with first cigarettes, and an increase in intestinal peristalsis. In very high doses appears a decrease of tone and motility.

According to doses, nicotine stimulates or inhibits various digestive and cutaneous secretions.

Action on neuromuscular junction

The action of nicotine on acetylcholine receptors of the neuromuscular synapse is much less important than that on ganglia of the autonomic nervous system. Nicotine in small dose facilitates neuromuscular transmission, which results in fasciculations of skeletal muscles; in very large doses, it tends to inhibit it.

Action on the central nervous system

Nicotine and tobacco, by their stimulant effect, seem to improve attention in monotonous tasks and to facilitate memorization. Nicotine, moreover, has anxiolytic and antinociceptive actions.

The lower frequency of Parkinson disease among smokers, compared with that of non smokers, has been explained by a possible inhibition of brain monoamine oxidase activity by nicotine.

Nicotine use induces tolerance i.e. diminution of its effects with a trend to increase its consumption and an addiction by increase of dopamine release making difficult cessation of tobacco..

The symptoms of tobacco withdrawal appear usually a few hours after its discontinuation, reach their maximum in a few days and last approximately a month.

In large doses, nicotine elicits tremors and seizures. Various compounds, in particular antiparkinsonian agents, can inhibit these symptoms.

In addition, nicotine has an antidiuretic action by stimulation antidiuretic hormone release.

Action on respiration

In animals an intravenous injection of nicotine elicits, by stimulation of the chemoreceptors of the carotid sinus, modifications of respiration, (apnea, stimulation, apnea). In toxic dose, nicotine causes respiratory depression being able to go until respiratory arrest.

Toxicity

The usual route of absorption of nicotine is respiratory for both active and passive smokers. A cigarette contains from 6 to 11 mg of nicotine of which 1 to 3 mg will be absorbed by pulmonary route. A digestive absorption of nicotine present in certain foods of vegetable origin is possible

Nicotine also exists in concentrated form in certain insecticides and, because of its caustic properties, it is quickly absorbed by all routes (oral, mucous and cutaneous) and can give rise to severe poisonings, particularly in non smokers because of the absence of tachyphylaxis.

In smokers, nicotine is responsible of a peripheral vasoconstriction and a rise in systolic and diastolic arterial pressure and increases cardiovascular risks. Tobacco use is disadvised, particularly in patients with cardiovascular diseases.

Lastly, let us recall that the tobacco increases considerably the risk of cancer of the respiratory routes, but among four thousand compounds present in tobacco smoke, nicotine is not the compound responsible for the carcinogenic effect of tobacco.

Therapeutic use

Nicotine is used to facilitate stopping smoking. It is marketed in the form of chewing gum and of devices for transdermal administration which ensure better and more regular absorption than intake by oral route. The nicotine intake decreases the need of smoking and facilitates smoking cessation, but it does not elicit a repulsion reaction for tobacco. Thus smokers should be informed that they must cease voluntarily smoking and that they do not feel an aversion effect for tobacco.

Note:

Analogues of nicotine could be of interest in the treatment of memory disorders.

Epibatidine is an alkaloid very powerful agonist of the nicotinic receptors which has a antinociceptive activity.


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  Last update : June 19, 2005  
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