Description: Nicotine is a naturally occurring alkaloid, long used by pharmacologists to investigate the autonomic nervous system. Nicotine by itself is not considered a health threat. Commercially, nicotine is complexed with polacrilin, a cationic resin, and is marketed as a chewing gum, and also as a transdermal patch. Nicotine chewing gum was approved by the FDA in January 1984, and transdermal patches were approved in November 1991. The patent for Nicorette® gum expired in 1994. The FDA approved nonprescription sale of the gum and the patches in February 1996 and July 1996, respectively. The first inhaled dosage form of nicotine, Nicotrol NS®, designed to be used as a nasal inhaler, was launched in September 1996. On May 5, 1997, the FDA approved a prescription-only oral inhalation system (Nicotrol® Inhaler). Nicotine transdermal systems (NTS) may be combined with the use of bupropion (Zyban®) for the treatment of psychological disorders, and the combined therapy received FDA approval in 1999. A less potent analog of nicotine, lobeline sulfate, is currently undergoing investigation.

Mechanism of Action: Nicotine's pharmacological actions are complex and include effects on both the central and peripheral nervous systems. Nicotine is classified as a stimulant of autonomic ganglia, although it possesses both stimulant and depressant actions. The end result of stimulation at what are now referred to as nicotinic receptors is a variety of cholinergic and adrenergic effects. These include: tachycardia or bradycardia mediated by either stimulation or interference with sympathetic or parasympathetic pathways, stimulation of receptors in the carotic and aortic bodies, release of epinephrine from the adrenal medulla, and stimulation of the chemoreceptor-trigger zone.

At the neuromuscular junction, nicotine is an agonist, but paralysis ensues due to receptor desensitization. The effects on the GI tract are secondary to parasympathetic stimulation.

Nicotine levels reach the brain within 7 seconds after a single drag, but peak concentrations can require as long as 4 hours after application of a patch. Chewing gum produces peak plasma concentrations within 15—20 minutes. . Nicotine is widely distributed in the body tissues, particularly the CNS.

The initial half-life is 2—3 minutes and the terminal half-life is 30—120 minutes, with considerable variation among individuals.