ArticleThe Biochemical journal2014
Kinetic characterization of human butyrylcholinesterase mutants for the hydrolysis of cocaethylene.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase.Scientific reports · 2024Article
- Long-lasting blocking of interoceptive effects of cocaine by a highly efficient cocaine hydrolase in rats.Scientific reports · 2024Article
- Gender differences in cocaine-induced hyperactivity and dopamine transporter trafficking to the plasma membrane.Addiction biology · 2022Article
- Recovery of dopaminergic system after cocaine exposure and impact of a long-acting cocaine hydrolase.Addiction biology · 2022Article
- Effects of alcohol on metabolism and toxicity of cocaine in rats.Toxicology reports · 2022Article
- Cocaine hydrolase blocks cocaine-induced dopamine transporter trafficking to the plasma membrane.Addiction biology · 2022Article
- Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine.Neuropharmacology · 2020Article
- Structure-Based Design and Discovery of a Long-Acting Cocaine Hydrolase Mutant with Improved Binding Affinity to Neonatal Fc Receptor for Treatment of Cocaine Abuse.The AAPS journal · 2020Article
- Catalytic activities of cocaine hydrolases against the most toxic cocaine metabolite norcocaethylene.Organic & biomolecular chemistry · 2020Article
- Reengineering of Albumin-Fused Cocaine Hydrolase CocH1 (TV-1380) to Prolong Its Biological Half-Life.The AAPS journal · 2019Article
- In vivo characterization of toxicity of norcocaethylene and norcocaine identified as the most toxic cocaine metabolites in male mice.Drug and alcohol dependence · 2019Article
- A latent class analysis of the past-30-day substance use patterns among lifetime cocaine users: Findings from a community sample in North Central Florida.Addictive behaviors reports · 2019Article
- Catalytic Reaction Mechanism for Drug Metabolism in Human Carboxylesterase-1: Cocaine Hydrolysis Pathway.Molecular pharmaceutics · 2018Article
- Effectiveness of a Cocaine Hydrolase for Cocaine Toxicity Treatment in Male and Female Rats.The AAPS journal · 2017Article
- A quantitative LC-MS/MS method for simultaneous determination of cocaine and its metabolites in whole blood.Journal of pharmaceutical and biomedical analysis · 2017Article
- Potential anti-obesity effects of a long-acting cocaine hydrolase.Chemico-biological interactions · 2016Article
- Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine.ACS chemical biology · 2016Article
- Long-acting cocaine hydrolase for addiction therapy.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Kinetic characterization of a cocaine hydrolase engineered from mouse butyrylcholinesterase.The Biochemical journal · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
It is known that the majority of cocaine users also consume alcohol. Alcohol can react with cocaine to produce a significantly more cytotoxic compound, cocaethylene. Hence a truly valuable cocaine-metabolizing enzyme as treatment for cocaine abuse/overdose should be efficient for not only cocaine itself, but also cocaethylene. The catalytic parameters (kcat and KM) of human BChE (butyrylcholinesterase) and two mutants (known as cocaine hydrolases E14-3 and E12-7) for cocaethylene are characterized in the present study, for the first time, in comparison with those for cocaine. On the basis of the obtained kinetic data, wild-type human BChE has a lower catalytic activity for cocaethylene (kcat=3.3 min(-1), KM=7.5 μM and kcat/KM=4.40 × 10(5) M(-1)·min(-1)) compared with its catalytic activity for (-)-cocaine. E14-3 and E12-7 have a considerably improved catalytic activity against cocaethylene compared with the wild-type BChE. E12-7 is identified as the most efficient enzyme for hydrolysing cocaethylene in addition to its high activity for (-)-cocaine. E12-7 has an 861-fold improved catalytic efficiency for cocaethylene (kcat=3600 min(-1), KM=9.5 μM and kcat/KM=3.79 × 10(8) M(-1)·min(-1)). It has been demonstrated that E12-7 as an exogenous enzyme can indeed rapidly metabolize cocaethylene in rats. Further kinetic modelling has suggested that E12-7 with an identical concentration as that of the endogenous BChE in human plasma can effectively eliminate (-)-cocaine, cocaethylene and norcocaine in simplified kinetic models of cocaine abuse and overdose associated with the concurrent use of cocaine and alcohol.
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