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

L. L. Howell, J. A. Nye, J. S. Stehouwer, R. J. Voll, J. Mun, D. Narasimhan, J. Nichols, R. Sunahara, M. M. Goodman, F. I. Carroll, J. H. Woods

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a KM of 1.33±0.085 μM. 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 [11C]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.

Original languageEnglish (US)
Article numbere407
JournalTranslational psychiatry
Volume4
DOIs
StatePublished - Jul 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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