(-)-COTININE Property

Melting point:

40-42 °C(lit.)

Boiling point:

250 °C150 mm Hg(lit.)

alpha 

[α]D20 -18～-22° (c=1, C2H5OH)

Density 

1.1102 (rough estimate)

refractive index 

1.7110 (estimate)

Flash point:

>230 °F

storage temp. 

Sealed in dry,2-8°C

solubility 

Chloroform (Sparingly), DMSO (Slightly), Methanol (Sparingly)

form 

Solid

pka

4.72±0.12(Predicted)

color 

Colourless to Very Dark Orange Oil

optical activity

[α]/D -21±2°, c = 1 in ethanol

Water Solubility 

Not miscible or difficult to mix in water. Soluble in dimethyl sulfoxide (100 mM), ethanol (50 mg/ml, yielding a clear, faint yellow to yellow solution), methanol and chloroform.

Merck 

14,2553

BRN 

83099

Stability:

Stable. Incompatible with strong oxidizing agents. May be heat sensitive - store cold.

EPA Substance Registry System

Cotinine (486-56-6)

Safety

Hazard Codes 

Xn,Xi,T,F

Risk Statements 

22-36/37/38-39/23/24/25-23/24/25-11

Safety Statements 

7-16-36/37-45-36-26

RIDADR 

UN 1230 3/PG 2

WGK Germany 

3

RTECS 

GN1925500

F 

10

HS Code 

29333990

Hazardous Substances Data

486-56-6(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

(-)-COTININE Chemical Properties,Usage,Production

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.

Chemical Properties

Colourless to Light Brown Solid

Uses

A major metabolite of nicotine in humans

Uses

A major metabolite of Nicotine (N412450) in humans. Carcinogen.

Uses

antidepressant

Uses

(-)-Cotinine is used to activate a subpopulation of α3/ α6β2 nAChRs in monkey striatum. It binds nicotinic- and muscarinic-type acetylcholine receptors with minimal receptor desensitization and demonstrates antipsychotic drug-like properties in behavioral models, neuroprotective properties in neurodegenerative disease models, and enhances attention in a delayed matching-to-sample task.

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.

Synthesis Reference(s)

Synthetic Communications, 18, p. 1331, 1988 DOI: 10.1080/00397918808078800

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 .

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.