A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates

A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K M of 1.33+0.085 μ M . In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE aga...

Full description

Saved in:
Bibliographic Details
Published in:Translational psychiatry 2014-07, Vol.4 (7), p.e407-e407
Main Authors: Howell, L L, Nye, J A, Stehouwer, J S, Voll, R J, Mun, J, Narasimhan, D, Nichols, J, Sunahara, R, Goodman, M M, Carroll, F I, Woods, J H
Format: Article
Language:English
Subjects:
59/78
631/378
Animals
Behavioral Sciences
Biological Psychology
Brain - diagnostic imaging
Brain - metabolism
Carboxylic Ester Hydrolases - administration & dosage
Carboxylic Ester Hydrolases - pharmacokinetics
Cocaine - pharmacokinetics
Drug Overdose - drug therapy
Enzyme Stability
Macaca mulatta
Medicine
Medicine & Public Health
Neurosciences
Original
original-article
Pharmacotherapy
Positron-Emission Tomography
Psychiatry
Recombinant Proteins - administration & dosage
Recombinant Proteins - pharmacokinetics
Rhodococcus - enzymology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K M of 1.33+0.085 μ M . In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [ 11 C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity.
ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2014.48