Cocaethylene

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Cocaethylene
Cocaethylene-2D-skeletal.png
Cocaethylene-3D-balls.png
Clinical data
Synonyms benzoylecgonine ethyl ester, ethylbenzoylecgonine,
Pregnancy
category
  • C
Dependence
liability
Moderate to high
Routes of
administration
Produced from ingestion of cocaine and ethanol
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
ECHA InfoCard 100.164.816 Edit this at Wikidata
Chemical and physical data
Formula C18H23NO4
Molar mass 317.38 g/mol
3D model (JSmol)

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 when cocaine and ethanol coexist in the blood.[1]

Metabolic production from cocaine[edit]

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 metabolitesbenzoylecgonine 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.[1]

cocaine + H2O → benzoylecgonine + methanol (with liver carboxylesterase 1)[2]
benzoylecgonine + ethanol → cocaethylene + H2O
cocaine + ethanol → cocaethylene + methanol (with liver carboxylesterase 1)[3]

Physiological effects[edit]

Cocaethylene is 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 a "triple reuptake inhibitor").[citation needed]

In most users, cocaethylene produces euphoria and has a longer duration of action than cocaine. Some studies[4] suggest that it may be more cardiotoxic than cocaine and "it also carries an 18- to 25-fold increase over cocaine alone in risk of immediate death".[5] Cocaethylene has a higher affinity for the dopamine transporter than does cocaine, but has a lower affinity for the serotonin and norepinephrine transporters.[6][7]

See also[edit]

References[edit]

  1. ^ a b Laizure SC, Mandrell T, Gades NM, Parker RB (January 2003). "Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases". Drug Metabolism and Disposition. 31 (1): 16–20. doi:10.1124/dmd.31.1.16. PMID 12485948. 
  2. ^ "MetaCyc Reaction: 3.1.1". Retrieved 25 January 2016. 
  3. ^ "MetaCyc Reaction: [no EC number assigned]". Retrieved 25 January 2016. 
  4. ^ Wilson LD, Jeromin J, Garvey L, Dorbandt A (March 2001). "Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse". Academic Emergency Medicine. 8 (3): 211–22. doi:10.1111/j.1553-2712.2001.tb01296.x. PMID 11229942. 
  5. ^ Andrews P (1997). "Cocaethylene toxicity". Journal of Addictive Diseases. 16 (3): 75–84. doi:10.1300/J069v16n03_08. PMID 9243342. 
  6. ^ Jatlow P, McCance EF, Bradberry CW, Elsworth JD, Taylor JR, Roth RH (August 1996). "Alcohol plus cocaine: the whole is more than the sum of its parts". Therapeutic Drug Monitoring. 18 (4): 460–4. doi:10.1097/00007691-199608000-00026. PMID 8857569. 
  7. ^ Perez-Reyes M, Jeffcoat AR, Myers M, Sihler K, Cook CE (December 1994). "Comparison in humans of the potency and pharmacokinetics of intravenously injected cocaethylene and cocaine". Psychopharmacology. 116 (4): 428–32. doi:10.1007/bf02247473. PMID 7701044. 

Further reading[edit]