Chemistry For Beating Down Cocaine Abuse

Two new research papers reveal biochemical details that could improve the prospects for treating cocaine overdose and addiction. In one study, Chang-Guo Zhan of the University of Kentucky and colleagues used a computational approach involving transition-state simulations to design an enzyme that breaks cocaine into biologically inactive metabolites (J. Am. Chem. Soc. 2008, 130, 12148). The enzyme is a mutant version of the body's own butyrylcholinesterase enzyme, but as the researchers observed, it is 2,000 times more efficient at metabolizing cocaine. The new enzyme prevented convulsions and death in mice given a cocaine overdose. In another study, Pascal Romieu of France's National Institute for Health & Medical Research, in Strasbourg, and coworkers focused on curbing cocaine dependence (J. Neurosci. 2008, 28, 9342). Drug abuse is believed to alter regulation of gene expression in part through deacetylation of histones, the proteins that DNA wraps around. The researchers reasoned that compounds that interfere with histone deacetylation might inhibit cocaine dependence. They showed that histone deacetylase inhibitors such as trichostatin A decreased the tendency of rats to take cocaine.