Format

Send to

Choose Destination
See comment in PubMed Commons below
Chem Biol Interact. 2008 Sep 25;175(1-3):83-7. doi: 10.1016/j.cbi.2008.04.024. Epub 2008 May 1.

An albumin-butyrylcholinesterase for cocaine toxicity and addiction: catalytic and pharmacokinetic properties.

Author information

1
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Abstract

Butyrylcholinesterase (BChE, EC 3.1.1.8) is important in human cocaine metabolism despite its limited ability to hydrolyze this drug. Efforts to improve the catalytic efficiency of this enzyme have led to a quadruple mutant cocaine hydrolase, "CocH", that in animal models of addiction appears promising for treatment of overdose and relapse. We incorporated the CocH mutations into a BChE-albumin fusion protein, "Albu-CocH", and evaluated the pharmacokinetics of the enzyme after i.v. injection in rats. As assessed from the time course of cocaine hydrolyzing activity in plasma, Albu-CocH redistributed into extracellular fluid (16% of estimated total body water) with a t(1/2) of 0.66h and it underwent elimination with a t(1/2) of 8h. These results indicate that the enzyme has ample stability for short-term applications and may be suitable for longer-term treatment as well. Present data also confirm the markedly enhanced power of Albu-CocH for cocaine hydrolysis and they support the view that Albu-CocH might prove valuable in treating phenomena associated with cocaine abuse.

PMID:
18514640
PMCID:
PMC2536750
DOI:
10.1016/j.cbi.2008.04.024
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center