Table 1.

Nicotine: Chemical, physical, biological characteristics and historical data.

Common Name	Nicotine
IUPAC Name	3-(1-methyl-2-pyrrolidinyl)pyridine
Chemical Specification	Bicyclic molecule characterized by a pyridine cycle and a pyrrolidine cycle existing in natures only in the S shape (i.e., levogyre) [1]
Chemical Characteristics	Chemical formula: C10H14N2 Molecular Weight: 162.234.
Physical Characteristics	Light yellow liquid that turns dark-brown after exposure to light/air with fishy odor when warm. Boiling point: 274.58 °C at 760 Tor [2]
Synthesized as SM by plants	Familia: Solanaceae, Genus: Nicotiana, Species: Nicotiana tabacum
History	1492 Cristoforo Colombo discovery of the plant Nicotiana. Nicotine owes is name to Jean Nicot (1530-1604) who introduced the use of tobacco to the French court (Caterina de Medici) in the sixteenth century, thus helping the spread of tobacco into all Europe [3] 1828 the German chemists Wilhelm Heinrich Posselt and Karl Ludwig Reimann were the first to isolate nicotine from tobacco. 1843 Louis Melsens described the chemical formula. 1893 Adolf Pinner and Richard Wolffenstein described the structure. 1904 Amé Pictet and Arnold Rotschy, synthesized nicotine [3]
Production, Use and Natural Resistance	Plants produce SM, metabolites not essential for plant reproduction, as direct defenses against pathogens (i.e., insects) and herbivores. Among SM, nicotine is one of the best-studied drug representing one of the first insecticides utilized to control pests in agriculture [4]. Although nicotine is very toxic, some insects develop resistance, indeed the tobacco hornworm Manduca sexta may survive to nicotine concentrations that are considered toxic for non-adapted herbivores [4]. Although the precise mechanisms for Manduca sexta’s nicotine resistance are not completely understood, an efficient excretion and metabolism seem to be involved. Manduca sexta uses nicotine to protect herself by the attack of its native major nocturnal predator wolf spider Camptocosa parallela [5]
Concentration in Tobacco leaves	The percentage of nicotine on dry weight of tobacco is between 0.3 to 8.3% depending on plant variety, as for Nicotiana gossei and Nicotiana velutina, respectively, and 6.7% in Virginia variety, and cultivation [6]
Lethal Doses	In animals the lethal dose may be from 3 mg/kg in mice to 50 mg/kg in rats. There is no consensus on the human lethal dose of nicotine and 60 mg of nicotine given orally (resulting in a plasma concentration of ~180 ng/mL) is often suggested as the lethal dose in the literature. However, it has been reported that adults may survive to dosages much higher than this (up to 500 mg) [7]
Metabolism	Nicotine is metabolized in the liver, principally to cotinine that in turn is metabolized to trans-3′-hydroxycotinine excreted via renal [8]
Nicotine concentrations into cigarette	The amount of nicotine in one tobacco cigarette is approximately 1–2% = 1–2 g/100. Considering the human body weight average equal to 68 kg one cigarette may deliver approximately 10–30 μg/Kg, resulting in a peak plasma level of 10–50 ng/mL. A concentration equal to 50 ng/mL can be converted to molarity dividing by nicotine MW (i.e., 162) (50 ng/mL divided by 162) = 0.309 = 3.1 × 10−7 M [9]. This concentration is 3.6 times lesser than the lethal dose. 60 mg dose means a 0.8 mg/kg in humans equivalent approximately to the amount found in five cigarettes.