Cocaethylene

Cocaethylene

Systematic (IUPAC) name
ethyl (2R,3S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
Clinical data
Pregnancy category	C
Legal status	UK: Controlled Drug Not scheduled specifically, could be prosecuted as an analogue of a scheduled substance.
Dependence liability	Moderate to High
Routes of administration	Produced from ingestion of cocaine and ethanol
Identifiers
CAS Number	529-38-4
ATC code	none
PubChem	CID: 65034
ChemSpider	559082
ChEMBL	CHEMBL608806
Synonyms	benzoylecgonine ethyl ester, ethylbenzoylecgonine,
Chemical data
Formula	C18H23NO4
Molecular mass	317.38 g/mol
SMILES O=C(O[C@H]1C[C@H]2N(C)[C@@H]([C@H]1C(=O)OCC)CC2)c3ccccc3

Cocaethylene (ethylbenzoylecgonine) is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed in vivo by the liver when cocaine and ethanol coexist in the blood.

Metabolic production from cocaine

Normally, cocaine's metabolism produces two primarily biologically inactive metabolites—benzoylecgonine and ecgonine methyl ester. The hepatic enzyme carboxylesterase is an important part of cocaine's metabolism because it acts as a catalyst for the hydrolysis of cocaine in the liver, which produces these inactive metabolites. If ethanol is present during the metabolism of cocaine, a portion of the cocaine undergoes transesterification with ethanol, rather than undergoing hydrolysis with water, which results in the production of cocaethylene.

cocaine + H₂O → benzoylecgonine + methanol (with liver carboxylesterase 1)

benzoylecgonine + ethanol → cocaethylene + H₂O

cocaine + ethanol → cocaethylene + methanol (with liver carboxylesterase 1)

Physiological effects

Cocaethylene is the byproduct of concurrent consumption of alcohol and cocaine as metabolized by the liver. Largely considered a recreational drug in and of itself; with stimulant, euphoriant, anorectic, sympathomimetic, and local anesthetic properties. The monoamine neurotransmitters serotonin, norepinephrine, and dopamine play important roles in cocaethylene's action in the brain. Cocaethylene increases the levels of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain by inhibiting the action of the serotonin transporter, norepinephrine transporter, and dopamine transporter. These pharmacological properties make cocaethylene a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) (also known as "triple reuptake inhibitor.")

In most users, cocaethylene produces euphoria and has a longer duration of action than cocaine. Some studies suggest that it may be more cardiotoxic than cocaine. Cocaethylene has a higher affinity for the dopamine transporter than does cocaine, but has a lower affinity for the serotonin and norepinephrine transporters.

Notes

Further reading

• Cocaethylene: responding to combined alcohol and cocaine use
• Warning of extra heart dangers from mixing cocaine and alcohol

See also

• Ethylphenidate
• Euphoriants
• Methylvanillylecgonine
• Local anesthetics
• Stimulants
• Tropanes
• Vin Mariani

• Cocaethylene metabolism : interaction with cocaine and ethanol Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases by Laizure SC, Mandrell T, Gades NM, Parker RB (January 31st, 2003).
• http://biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13424
• http://biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13425