Cocaethylene
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Cocaethylene (ethylbenzoylecgonine) is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed by the liver in small amounts when cocaine and ethanol coexist in the blood.<ref name="Laizure et al 2003">Template:Cite journal</ref> In 1885, cocaethylene was first synthesized (according to edition 13 of the Merck Index),<ref name="pmid30796807">Template:Cite journal</ref> and in 1979, cocaethylene's side effects were discovered.<ref>* {{#invoke:citation/CS1|citation |CitationClass=web }} </ref>
Metabolic production from cocaineEdit
Cocaethylene is the byproduct of concurrent consumption of alcohol and cocaine as metabolized by the liver. Normally, metabolism of cocaine 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.<ref name="Laizure et al 2003"/>
- cocaine + H2O → benzoylecgonine + methanol (with liver carboxylesterase 1)<ref>{{#invoke:citation/CS1|citation
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- benzoylecgonine + ethanol → cocaethylene + H2O
- cocaine + ethanol → cocaethylene + methanol (with liver carboxylesterase 1)<ref>{{#invoke:citation/CS1|citation
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Physiological effectsEdit
Cocaethylene increases the levels of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain and has a higher affinity for the dopamine transporter than cocaine, but has a lower affinity for the serotonin and norepinephrine transporters.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> These pharmacological properties make cocaethylene a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI; also known as a "triple reuptake inhibitor").<ref>Template:Cite journal</ref>
Although it cannot be bought, cocaethylene is largely considered recreational in and of itself, with stimulant, euphoriant, anorectic, sympathomimetic, and local anesthetic properties with a longer duration of action than cocaine.<ref name="Original_Investigation">Template:Cite journal</ref><ref name="J_Addict_Dis">Template:Cite journal</ref> 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.<ref name="Original_Investigation" />
RisksEdit
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".<ref name="ACMDReport">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Some studies<ref>Template:Cite journal</ref><ref name="Farre">Template:Cite journal</ref> 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".<ref name="J_Addict_Dis" />
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.<ref>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</ref>
See alsoEdit
- Ethylphenidate
- Euphoriants
- Methylvanillylecgonine
- Local anesthetics
- RTI-160
- Stimulants
- Tropanes
- Vin Mariani
- Pemberton's French Wine Coca
ReferencesEdit
Further readingEdit
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