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Cotinine is an alkaloid found in tobacco and is also a metabolite of nicotine. The word "cotinine" is an anagram of "nicotine". Cotinine is used as a biomarker for exposure to tobacco smoke. Cotinine was developed as an antidepressant as a fumaric acid salt, cotinine fumarate, to be sold under the brand name Scotine. It was never marketed. 
Similarly to nicotine, cotinine binds to, activates, and desensitizes neuronal nicotinic acetylcholine receptors, though at much lower potency in comparison. It has demonstrated nootropic and antipsychotic-like effects in animal models. Direct administration of high levels of cotinine resulted in no significant physiologic, subjective, or performance effects.
Measure of cotinine exposure
Cotinine has an in vivo half-life of approximately 20 hours, and is typically detectable for several days (up to one week) after the use of tobacco. The level of cotinine in the blood, saliva, and urine is proportionate to the amount of exposure to tobacco smoke, so it is a valuable indicator of tobacco smoke exposure, including secondary (passive) smoke. People who smoke menthol cigarettes may retain cotinine in the blood for a longer period because menthol can compete with enzymatic metabolism of cotinine. African Americans generally have higher plasma cotinine levels than Caucasians, males generally have higher plasma cotinine levels than females. These systematic differences in cotinine levels were attributed to variation in CYP2A6 activity. At steady state, plasma cotinine levels are determined by the amount of cotinine formation and the rate of cotinine removal, which are both mediated by the enzyme CYP2A6. Since CYP2A6 activity differs by sex (estrogen induces CYP2A6) and race (due to genetic variation), cotinine accumulates in individuals with slower CYP2A6 activity, resulting in substantial differences in cotinine levels for a given tobacco exposure.
Cotinine levels <10 ng/mL are considered to be consistent with no active smoking. Values of 10 ng/mL to 100 ng/mL are associated with light smoking or moderate passive exposure, and levels above 300 ng/mL are seen in heavy smokers - more than 20 cigarettes a day. In urine, values between 11 ng/mL and 30 ng/mL may be associated with light smoking or passive exposure, and levels in active smokers typically reach 500 ng/mL or more. In saliva, values between 1ng/ml and 30 ng/ml may be associated with light smoking or passive exposure, and levels in active smokers typically reach 100 ng/ml or more. Cotinine assays provide an objective quantitative measure that is more reliable than smoking histories or counting the number of cigarettes smoked per day. Cotinine also permits the measurement of exposure to second-hand smoke (passive smoking).
Drug tests can detect cotinine in the blood, urine, or saliva. Salivary cotinine concentrations are highly correlated to blood cotinine concentrations, and can detect cotinine in a low range, making it the preferable option for a less invasive method of tobacco exposure testing. Urine cotinine concentrations average fourfold to sixfold higher than those in blood or saliva, making urine a more sensitive matrix to detect low-concentration exposure.
However, nicotine replacement therapies (i.e., gum, lozenge, patch, inhaler, and nasal spray) used to help tobacco users quit contain nicotine. Use of nicotine replacement therapy will result in a positive test for cotinine. Therefore, the presence of cotinine is not a conclusive indication of tobacco use.
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