Cotinine

Source: Wikipedia, the free encyclopedia.

Cotinine
Clinical data
Routes of
administration
Oral, Smoked, Insufflation
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life20 hours
Identifiers
  • (5S)-1-methyl-5-(3-pyridyl)pyrrolidin-2-one
JSmol)
  • O=C2N(C)[C@H](c1cnccc1)CC2
  • InChI=1S/C10H12N2O/c1-12-9(4-5-10(12)13)8-3-2-6-11-7-8/h2-3,6-7,9H,4-5H2,1H3/t9-/m0/s1 checkY
  • Key:UIKROCXWUNQSPJ-VIFPVBQESA-N checkY
  (verify)

Cotinine is an alkaloid found in tobacco[1] and is also the predominant metabolite of nicotine,[2][3] typically used as a biomarker for exposure to tobacco smoke. Cotinine is currently being studied as a treatment for depression, post-traumatic stress disorder (PTSD), schizophrenia, Alzheimer's disease and Parkinson's disease. Cotinine was developed as an antidepressant as a fumaric acid salt, cotinine fumarate, to be sold under the brand name Scotine, but it was never marketed.[2]

Similarly to nicotine, cotinine binds to, activates, and desensitizes neuronal nicotinic acetylcholine receptors, though at much lower potency in comparison.[3][4][5][6] It has demonstrated nootropic and antipsychotic-like effects in animal models.[7][8] Cotinine treatment has also been shown to reduce depression, anxiety, and fear-related behavior as well as memory impairment in animal models of depression, post-traumatic stress disorder, and Alzheimer's disease.[9] Nonetheless, treatment with cotinine in humans was reported to have no significant physiologic, subjective, or performance effects in one study,[10] though others suggest that this may not be the case.[11]

Because cotinine is the main metabolite to nicotine and has been shown to be pharmacologically active, it has been suggested that some of nicotine's effects in the nervous system may be mediated by cotinine and/or complex interactions with nicotine itself.[9][12]

Pharmacology

A few studies indicate that the affinity for cotinine to the nicotinic acetylcholine receptors (nAChRs) is about 100 times lower than nicotine's.[11] Some work suggests that cotinine may be a positive allosteric modulator of α7 nAChRs.[13][11] If this is true, cotinine would facilitate endogenous neurotransmission without directly stimulating nAChRs.

Pharmacokinetics

Cotinine has an

Caucasian smokers.[16] Males generally have higher plasma cotinine levels than females.[17] These systematic differences in cotinine levels were attributed to variation in CYP2A6 activity.[18] 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.[18] Since CYP2A6 activity differs by sex (estrogen induces CYP2A6) and genetic variation, cotinine accumulates in individuals with slower CYP2A6 activity, resulting in substantial differences in cotinine levels for a given tobacco exposure.[18]

Detection in body fluids

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 four to six times higher than those in blood or saliva, making urine a more sensitive matrix to detect low-concentration exposure.[19]

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 1 ng/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.[20] 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).

However, tobacco users attempting to quit with the help of nicotine replacement therapies (i.e., gum, lozenge, patch, inhaler, and nasal spray) will also test positive for cotinine, since all common NRT therapies contain nicotine that is metabolized in the same way. Therefore, the presence of cotinine is not a conclusive indication of tobacco use.

e-cigarettes, where laboratory smoking machines have many problems replicating real-life conditions.[22]

Serum cotinine concentration has been used for decades in US population

blacks
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References

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  15. ^ Ham B (December 2002). "Signs of smoking linger longer in menthol smokers". Center for the Advancement of Health. Science Blog. Archived from the original on 26 June 2010. Retrieved 17 March 2010.
  16. PMID 2382740
    .
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  18. ^ .
  19. ^ Avila-Tang, Erika et al (September 2012). "Assessing secondhand smoke using biological markers" - Nicotine and metabolites [1]. Retrieved 10 June 2013
  20. PMID 18783507
    .
  21. ^ Hewitt D. "Reasons for False Positives for Nicotine on a Blood Test". LiveStrong.com. Retrieved 21 October 2011.
  22. ^ McNeil A, Brose LS, Calder R, Hitchman SC, Hajek P, McRobbie H (2015). "E-cigarettes: an evidence update. A report commissioned by Public Health England" (PDF). Gov.uk. UK: Public Health England. pp. 70–75. Retrieved 20 August 2015.
  23. PMID 30521502
    .