nicotine is a simple alkaloid produced by the tobacco plant. The history of chewing and smoking tobacco, and of taking snuff, is of great antiquity. All the acute effects of the tobacco habit are dependent on nicotine, which has complex actions, both on the central nervous system and in the rest of the body. Nicotine acts on certain cell membrane receptors, which were therefore given the name nicotinic receptors. Nicotine was found to mimic the actions of the neurotransmitter acetylcholine at these sites: at the neuromuscular junctions in skeletal (voluntary) muscle; at the synapses in the relay stations (the ganglia) of the autonomic nervous system; and in various parts of the brain and spinal cord. In many situations nicotine first activates the nicotinic receptors and then by its continued presence desensitizes them. Normally, at these nicotinic synapses, the transmitter (acetylcholine) is rapidly destroyed by the enzyme cholinesterase, so its action is evanescent; this is not the case with nicotine.

Nicotinic receptors are proteins which span the cell membrane (e.g. of a muscle cell or neuron) and when activated by acetylcholine or by nicotine undergo a conformational change that creates ion channels in the membrane. These channels allow the passage of sodium ions inwards and potassium ions outwards through the membrane, leading to excitation of the cell.

Increased levels of nicotine can be measured in the blood up to one hour after a cigarette. Nicotine-taking, in whatever form, is for self gratification and reward, requiring reinforcement at intervals. If nicotine is withdrawn, irritability and failure to concentrate is the result. The actions of nicotine are caused by effects in the brain. Repeated intake of nicotine leads to increased numbers of nicotinic receptors in the brain, which might be expected to reduce the need for nicotine rather than increase it. But it seems likely that many of the receptors are in a desensitized form and that the number of functional receptors is reduced, so that the addict requires increasing and repeated doses to maintain the effect. The claims that nicotine increases concentration, learning ability, and retention of learned information are well founded — numbers of performance tests have confirmed this. Nicotine produces a sense of alertness, but nevertheless of calm. This seems to be due to inhibition of reflex nerve loops in the spinal cord, with the effect of causing muscular relaxation.

The above actions all take place in the central nervous system. The effects of nicotine in the rest of the body are due to actions on the ganglia of the autonomic nervous system, predominantly on the sympathetic ganglia. Mimicking the effects of physiological sympathetic stimulation, they include increases in heart rate, cardiac output, and blood pressure, and reduction in gut motility and digestive functions. Because the adrenal medulla is a modified sympathetic ganglion — with secretion normally stimulated by acetylcholine — adrenaline and noradrenaline are released by the action of nicotine; these are likely to be responsible for most of the cardiovascular effects. Nicotine also releases antidiuretic hormone from the posterior pituitary gland, hence reducing the formation of urine.

Nicotine is not used therapeutically, except for nicotine patches and chewing gum, which are used to help smokers give up the habit. They do not have the dangers associated with constituents of tobacco smoke.

For some time nicotine enjoyed popularity as an insecticide. However, in its concentrated form it is highly poisonous, and it can be absorbed through the skin, so is no longer used for spraying on plants. Lobeline, another plant alkaloid from Lobelia species, has very similar actions to nicotine.

Alan W. Cuthbert

See also acetylcholine; autonomic nervous system; neurotransmitters; membrane receptors; smoking.