Blocking drug activation as a therapeutic strategy to attenuate acute toxicity and physiological effects of heroin.

Heroin is a growing national crisis in America. There is an increasing frequency of heroin overdoses. All of the currently used therapeutic approaches to treatment of heroin abuse and other opioid drugs of abuse focus on antagonizing a brain receptor (particularly µ-opiate receptors). However, it has been known that the therapeutic use of certain µ-opiate receptor antagonist may actually increase heroin overdose. Once overdosed, heroin addicts may continue to get overdosed again and again until fatal. Here we report our design and validation of a novel therapeutic strategy targeting heroin activation based on our analysis of the chemical transformation and functional change of heroin in the body. An effective blocker of heroin activation, such as ethopropazine tested in this study, may be used as a standalone therapy or in combination with a currently available, traditional medications targeting µ-opiate receptors (e.g. naltrexone or its extended-release formulation Vivitrol). The combination therapy would be ideal for heroin abuse treatment as the effects of two therapeutic agents targeting two independent mechanisms are cooperative.