Cocaethylene: A Unique Cocaine Metabolite Displays High Affinity for the Dopamine Transporter

TLDR

Concurrent cocaine and alcohol use is common, and when ethanol is present, cocaine is metabolized to the ethyl homolog cocaethylene. Cocaethylene forms via a liver transesterification of cocaine and ethanol, a novel metabolic reaction. Cocaethylene is detected in blood, liver, and brain at concentrations comparable to or exceeding cocaine, binds monoamine transporters similarly to cocaine, is equipotent at the dopamine transporter, and its dopamine reuptake blockade likely underlies the heightened euphoria seen with combined alcohol and cocaine use.

Abstract

Abstract: Concurrent cocaine and alcohol use is common practice in the general population, as indicated by recent prevalence studies. In the presence of ethyl alcohol, cocaine is metabolized to its ethyl homolog, cocaethylene. The transesterification of cocaine and ethanol to cocaethylene takes place in the liver and represents a novel metabolic reaction. Cocaethylene was detected in postmortem blood, liver, and neurological tissues in concentrations equal to and sometimes exceeding those of cocaine. In vitro binding studies demonstrate that cocaethylene has a pharmacological profile similar but not identical to that of cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was equipotent to cocaine at inhibiting [ 3 H]mazindol binding to the dopamine transporter. The blockade of dopamine reuptake in the synaptic cleft by cocaethylene may account for the enhanced euphoria associated with combined alcohol and cocaine abuse.