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 journalArticle

97 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 1 2008

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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