A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats

Stephen Brimijoin, Yang Gao, Justin J. Anker, Luke A. Gliddon, David LaFleur, R. Shah, Qinghai Zhao, M. Singh, Marilyn E. Carroll

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even when administered after the drug, and provided rescue after convulsions commenced. Moreover, it selectively blocked cocaine-induced reinstatement of drug seeking in rats that had previously self-administered cocaine. The enzyme treatment was well tolerated and may be worth exploring for clinical application in humans.

Original languageEnglish (US)
Pages (from-to)2715-2725
Number of pages11
JournalNeuropsychopharmacology
Volume33
Issue number11
DOIs
StatePublished - Oct 2008

Bibliographical note

Funding Information:
The research in this article was supported by a grant from the Minnesota Partnership for Medical Genomics and Biotechnology and by grant R01-DA023979-01 from NIH/ NIDA. Additional funds were provided by Cogenesys Inc., Rockville, MD, which generated the material under study. Four of the authors (DL, RS, QZ, and MS) are employees of Cogenesys.

Keywords

  • Addiction relapse
  • Albumin fusion proteins
  • Cocaine overdose rescue
  • Drug self-administration rodent model
  • Operant conditioning
  • Protein-based therapeutics for cocaine abuse

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