Chemical Properties
Colourless to Light Brown Solid
Uses
A major metabolite of Nicotine (N412450) in humans. Carcinogen.
Uses
A major metabolite of nicotine in humans
Definition
ChEBI: An N-alkylpyrrolidine that consists of N-methylpyrrolidinone bearing a pyridin-3-yl substituent at position C-5 (the 5S-enantiomer). It is an alkaloid commonly found in Nicotiana tabacum.
Biological Activity
Major metabolite of nicotine. Shown to activate a subpopulation of α 3/ α 6 β 2 nAChRs in monkey striatum. Displays cognition-enhancing effects in vivo .
Description
Cotinine is the major metabolite of nicotine. In the liver,
nicotine is rapidly metabolized to cotinine (70–80%) by
CYP2A6 and to nornicotine (5%) by CYP2A6 and CYP2B6.
With a half-life about 10-fold longer than that of nicotine
(15–19 h for cotinine versus 2–3 h for nicotine), cotinine
induces plasma concentrations of 1–3 mM in smokers. After
administration to rats, cotinine levels in the brain reach
fourfold those of nicotine at 4 h following injection. Cotinine
is not biotransformed in the brain, allowing accumulation
of this substance to levels greater than that of
nicotine.
Like nicotine, cotinine is able to induce dopamine release in
smokers and in superfused rat striatal slices in a dose- and
calcium-dependent manner via the nicotinic receptors, but
only at concentrations higher than those normally seen in
smokers. Indeed, administration of cotinine to smokers at
levels 10-fold that is seen following smoking had no observable
effect, suggesting that cotinine is not neuroactive at doses
found in smokers. However, cotinine also acts as an inhibitor
for nicotine binding in rat brain via desensitization of the
nicotinic receptor.
Environmental Fate
Cotinine stimulates dopamine release in the nigrostriatal
pathway by activating nicotinic acetylcholine receptors.
However, its lower EC50 prevents significant activation of this
pathway in smokers.
Toxicity evaluation
Cotinine has a vapor pressure of 3.8×10-4mmHg at 25 °C.
Cotinine will be photochemically degraded with a half-life of
15 h. In sediment, cotinine is completely degraded to carbon
dioxide within 72 h. It is not expected to bioaccumulate in
aquatic organisms.
