Cocaethylene (ethylbenzoylecgonine) is the ethyl

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of benzoylecgonine. It is structurally similar to

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

, which is the methyl ester of benzoylecgonine. Cocaethylene is formed by the liver in small amounts when cocaine and

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

coexist in the blood. In 1885, cocaethylene was first synthesized (according to edition 13 of the ''

Merck Index ''The Merck Index'' is an encyclopedia of chemical substance, chemicals, pharmaceutical drug, drugs and biomolecule, biologicals with over 10,000 monographs on single substances or groups of related chemical compound, compounds published online ...

''), and in 1979, cocaethylene's side effects were discovered.

Metabolic production from cocaine

Cocaethylene is the byproduct of concurrent consumption of

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

and

as metabolized by the liver. Normally, metabolism of cocaine produces two primarily biologically inactive

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

— 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 Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

of cocaine in the liver, which produces these inactive metabolites. If

is present during the metabolism of cocaine, a portion of the cocaine undergoes transesterification with ethanol, rather than undergoing hydrolysis with

water Water is an inorganic compound with the chemical formula . It is a transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance. It is the main constituent of Earth's hydrosphere and the fluids of all known liv ...

, which results in the production of cocaethylene. :cocaine + H₂O → benzoylecgonine +

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

(with liver carboxylesterase 1) :benzoylecgonine + ethanol → cocaethylene + H₂O :cocaine + ethanol → cocaethylene +

(with liver carboxylesterase 1)

Physiological effects

Cocaethylene increases the levels of serotonergic, noradrenergic, and

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurotransmission in the brain and has a higher

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for the dopamine transporter than cocaine, but has a lower affinity for the serotonin and norepinephrine transporters. These pharmacological properties make cocaethylene a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI; also known as a "triple reuptake inhibitor"). Although it cannot be bought, cocaethylene is largely considered recreational in and of itself, with

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

, euphoriant, anorectic, sympathomimetic, and

local anesthetic A local anesthetic (LA) is a medication that causes absence of all sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensati ...

properties with a longer duration of action than cocaine. A 2000 study by Hart et al. on the effects of intravenous cocaethylene in humans found that "cocaethylene has pharmacological properties in common with cocaine, but is less potent," consistent with prior research.

Risks

While cocaethylene is more dangerous when administered alone, research suggests that the increase in risk from combining cocaine and ethanol is "thought to be due to alcohol decreasing the metabolism of cocaine and, therefore, increasing ..cocaine concentrations with only a minimal (if any) contribution to an increased risk from the formation of cocaethylene". Some studies suggest that consuming alcohol in combination with cocaine may be more cardiotoxic than cocaine and "it also carries an 18 to 25 fold increase over cocaine alone in risk of immediate death". Additionally, studies have determined that cocaethylene has a higher hepatoxicity than alcohol or cocaine and their respective metabolites alone, significantly increasing the risk of

liver fibrosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

.Tamargo, J. A., Sherman, K. E., Sékaly, R. P., Bordi, R., Schlatzer, D., Lai, S., Khalsa, J. H., Mandler, R. N., Ehman, R. L., & Baum, M. K. (2022). Cocaethylene, simultaneous alcohol and cocaine use, and liver fibrosis in people living with and without HIV. Drug and alcohol dependence, 232, 109273. https://doi.org/10.1016/j.drugalcdep.2022.109273

Metabolic production from cocaine

Physiological effects

Risks

See also

References

Further reading