Cotinine

Not to be confused with cotinin.

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
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.941 Edit this at Wikidata
Chemical and physical data
FormulaC10H12N2O
Molar mass176.219 g·mol−1
3D model (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]

  1. ^ Laszlo C, Kaminski K, Guan H, Fatarova M, Wei J, Bergounioux A, Schlage WK, Schorderet-Weber S, Guy PA, Ivanov NV, Lamottke K, Hoeng J (November 2022). "Fractionation and Extraction Optimization of Potentially Valuable Compounds and Their Profiling in Six Varieties of Two Nicotiana Species". Molecules. 27 (22): 8105. doi:10.3390/molecules27228105. PMC 9694777. PMID 36432206.
  2. ^ a b Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 978-0-412-46630-4.
  3. ^ a b Dwoskin LP, Teng L, Buxton ST, Crooks PA (March 1999). "(S)-(-)-Cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H]dopamine release from rat striatal slices in a calcium-dependent manner". The Journal of Pharmacology and Experimental Therapeutics. 288 (3): 905–911. PMID 10027825.
  4. ^ Anderson DJ, Arneric SP (March 1994). "Nicotinic receptor binding of [3H]cytisine, [3H]nicotine and [3H]methylcarbamylcholine in rat brain". European Journal of Pharmacology. 253 (3): 261–267. doi:10.1016/0014-2999(94)90200-3. PMID 8200419.
  5. ^ Briggs CA, McKenna DG (September 1998). "Activation and inhibition of the human alpha7 nicotinic acetylcholine receptor by agonists". Neuropharmacology. 37 (9): 1095–1102. doi:10.1016/S0028-3908(98)00110-5. PMID 9833639. S2CID 45834866.
  6. ^ Buccafusco JJ, Shuster LC, Terry AV (February 2007). "Disconnection between activation and desensitization of autonomic nicotinic receptors by nicotine and cotinine". Neuroscience Letters. 413 (1): 68–71. doi:10.1016/j.neulet.2006.11.028. PMID 17157984. S2CID 6859655.
  7. ^ Buccafusco JJ, Terry AV (October 2009). "A reversible model of the cognitive impairment associated with schizophrenia in monkeys: potential therapeutic effects of two nicotinic acetylcholine receptor agonists". Biochemical Pharmacology. 78 (7): 852–862. doi:10.1016/j.bcp.2009.06.102. PMC 2728139. PMID 19577545.
  8. ^ Buccafusco JJ, Beach JW, Terry AV (February 2009). "Desensitization of nicotinic acetylcholine receptors as a strategy for drug development". The Journal of Pharmacology and Experimental Therapeutics. 328 (2): 364–370. doi:10.1124/jpet.108.145292. PMC 2682277. PMID 19023041.
  9. ^ a b Grizzell JA, Echeverria V (October 2015). "New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine". Neurochemical Research. 40 (10): 2032–2046. doi:10.1007/s11064-014-1359-2. PMID 24970109. S2CID 9393548.
  10. ^ Hatsukami DK, Grillo M, Pentel PR, Oncken C, Bliss R (August 1997). "Safety of cotinine in humans: physiologic, subjective, and cognitive effects". Pharmacology, Biochemistry, and Behavior. 57 (4): 643–650. doi:10.1016/s0091-3057(97)80001-9. PMID 9258989. S2CID 13460499.
  11. ^ Moran VE (October 2012). "Cotinine: Beyond that Expected, More than a Biomarker of Tobacco Consumption". Frontiers in Pharmacology. 3: 173. doi:10.3389/fphar.2012.00173. PMC 3467453. PMID 23087643.
  12. ^ Crooks PA, Dwoskin LP (October 1997). "Contribution of CNS nicotine metabolites to the neuropharmacological effects of nicotine and tobacco smoking". Biochemical Pharmacology. 54 (7): 743–753. doi:10.1016/s0006-2952(97)00117-2. PMID 9353128.