Nicotine has an agonistic action at the nicotinic receptor sites in the cholinergic nervous system. It binds with these receptors in a similar manner as acetylcholine (ACh), predominantly at the midbrain level, and influences various reflexes by excitation of chemoreceptors in the carotid body.

The effects of nicotine are described in terms of a sense of alertness, relaxation, pleasure, increased concentration, and stimulation of the autonomic nervous system.

Prolonged use of nicotine causes a significant increase in the number of nicotinic receptors, and in the accumulation of ACh by enzymatic induction and/or repression of choline acetyltransferase (CAT) and acetylcholinesterase (AChE). The overall result is biochemical tolerance, and physiological and psychological dependence.

During nicotine abstinence in chronic smokers, the biochemical interpretation of withdrawal is through the elimination of the nicotine blockade at nicotinic sites. Withdrawal symptoms result from excessive ACh intersynaptic stimulation of predominately muscarinic receptors in the Nucleus Accumbens and Ventral Tegmental Area. The responses may result in excitation or inhibition, and the clinical symptoms can include decreased heart rate and blood pressure, gastrointestinal disturbances, fatigue, nausea, headache, and electroencephalogram changes, along with increased irritability, nervousness, and decreased concentration.

Injections of scopolamine and atropine provide effective levels of anticholinergic activity to block the attachment of ACh to these receptors, thereby reducing and eliminating physical nicotine withdrawal symptoms during their most pronounced period - the first 24 to 48 hours of abstinence.

Although nicotine is eliminated from the body by urination in approximately three days, the normalization of ACh concentrations to non-smoker status can take up to two weeks. Consequently, oral and transdermal anticholinergic treatment is prescribed during this two week period to maintain lower, yet therapeutically effective, levels while withdrawal symptoms subside.

Treatment is supported by an interactive program of self-help behavioral changes to maintain nicotine abstinence permanently.

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