Cocaethylene
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| Systematic (IUPAC) name | |
|---|---|
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ethyl (2R,3S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
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| Clinical data | |
| Pregnancy category |
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| Legal status |
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| Dependence liability |
Moderate to High |
| Routes of administration |
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 |
| Molecular mass | 317.38 g/mol |
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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 in vivo by the liver when cocaine and ethanol coexist in the blood.[1]
Contents
Metabolic production from cocaine[edit]
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[edit]
Cocaethylene is the byproduct of concurrent consumption of alcohol and cocaine as metabolized by the liver. 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 "triple reuptake inhibitor.")
In most users, cocaethylene produces euphoria and has a longer duration of action than cocaine. Some studies[5] 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.[6][7]
Notes[edit]
References[edit]
- ^ 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.
- ^ 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).
- ^ http://biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13424
- ^ http://biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13425
- ^ Wilson, L. D.; Jeromin, J; Garvey, L; Dorbandt, A (2001). "Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse". Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 8 (3): 211–22. doi:10.1111/j.1553-2712.2001.tb01296.x. PMID 11229942.
- ^ 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" Check
|url= - ^ 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[edit]
- Cocaethylene: responding to combined alcohol and cocaine use
- M. J. Landry (1992). "An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite". J. Psychoactive Drugs 24 (3): 273–6. doi:10.1080/02791072.1992.10471648. PMID 1432406.
- Warning of extra heart dangers from mixing cocaine and alcohol
- Hearn, WL; Rose, S; Wagner, J; Ciarleglio, A; Mash, DC (1991). "Cocaethylene is more potent than cocaine in mediating lethality". Pharmacology, Biochemistry, and Behavior 39 (2): 531–3. doi:10.1016/0091-3057(91)90222-N. PMID 1946594.
- Hearn, WL; Flynn, DD; Hime, GW; Rose, S; Cofino, JC; Mantero-Atienza, E; Wetli, CV; Mash, DC (1991). "Cocaethylene: A unique cocaine metabolite displays high affinity for the dopamine transporter". Journal of Neurochemistry 56 (2): 698–701. doi:10.1111/j.1471-4159.1991.tb08205.x. PMID 1988563.
