Cocaethylene

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Cocaethylene
Systematic (IUPAC) name
ethyl (2R,3S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
Clinical data
Pregnancy cat. C
Legal status CD (UK) Not scheduled specifically, could be prosecuted as an analogue of a scheduled substance.
Dependence liability Moderate to High
Routes 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 
Mol. mass 317.38 g/mol

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.[1]

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.[2]

cocaine + H2O → benzoylecgonine + methanol (with liver carboxylesterase 1)[3]
benzoylecgonine + ethanol → cocaethylene + H2O
cocaine + ethanol → cocaethylene + methanol (with liver carboxylesterase 1)[4]

Physiological effects

Cocaethylene is a recreational drug 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.")

Cocaethylene appears to, in most users, produce euphoria, and possess 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.[5][6]

Notes

References

  1. ↑ S. Casey Laizure, Timothy Mandrell, Naomi M. Gades, and Robert B. Parker (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. ↑ 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).
  3. ↑ http://biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13424
  4. ↑ http://biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13425
  5. ↑ Jatlow, Peter; McCance, Elinore F.; Bradberry, Charles W.; Elsworth, John D.; Taylor, Jane R.; Roth, Robert H. (1996). noradrenaline transporter(NAT) 00026&type=abstract "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. 
  6. ↑ M. Perez et al. (1994). "Cocaine and cocaethylene: microdialysis comparison of brain drug levels and effects on dopamine and serotonin". Psychopharmacology (Berl.) 116 (4): 428–32. doi:10.1111/j.1471-4159.1993.tb03305.x. PMID 8455033. 

Further reading

See also

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