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GLT-1 enhancers for the treatment of cocaine addiction

Approximately 1 million Americans meet the criteria for cocaine use disorder (CUD) (Center for Behavioral Health Statistics and Quality, 2015).  While many cocaine users are able to attain long periods of drug abstinence, approximately 85% of users relapse, typically when exposed to cocaine-paired cues or stress or after taking a small amount of the drug again (Bossert et al, 2005; Epstein et al, 2006; O’Brien, 2003).  There are currently no FDA-approved medications to reduce the risk of relapse. It has been previously demonstrated that the major glutamate transporter GLT-1 expression is decreased upon chronic exposure to cocaine.  In addition, some, but not all, members of the β-lactam family of antibiotics were found to restore GLT-1 expression in animal models.  Ceftriaxone was the most potent in this class of antibiotics. As part of our on-going efforts to explore the utility of GLT-1 expression enhancers, we have developed a series of novel, potent, non-antibiotic b-lactams capable of up-regulating GLT-1 expression in animal models of cocaine addiction.

Temple University
Moulder Center for Drug Discovery Research

Temple University School of Pharmacy
3307 N Broad Street
Philadelphia, PA 19140