Pharmacology and Therapy for MDPV and alpha-PVP Like Drugs of Abuse

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 DESCRIPTION (provided by applicant): Abuse of the class of illicit drugs known as cathinones or "bath salts" is a dangerous and growing worldwide problem. This project will focus on two medically important cathinones, MDPV and alpha-PVP. These two designer psychostimulant drugs were chosen because they are most often associated with human abuse and toxicity. Through their actions as dual reuptake inhibitors of norepinephrine and dopamine they elicit CNS effects, cardiovascular (CV) hypertension and tachycardia, agitation, seizures, violent behaviors, and death. Scientific evidence suggests the (S)-isomers of MDVP and alpha-PVP are the most potent stereoisomers for producing CNS psychoactive stimulant effects. Thus, we hypothesize that treatment of racemic MDPV or alpha-PVP toxicity with a high affinity monoclonal antibody (mAb) against (S)-MDPV and (S)-alpha-PVP can protect abusers from harmful psychoactive stimulant effects. We will also determine which isomer(s) cause CV toxicity, and generate mAb medications against the most active isomeric form. The specific aims include 1) development of important endpoints for assessing anti-cathinone mAb therapeutic efficacy in male and female rats, 2) synthesis of novel cathinone-like antigenic haptens for use in making a high affinity anti-MDPV and alpha-PVP mAb, 3) testing of the ability of these new therapies to reduce MDPV- and alpha-PVP-induced adverse effects in male and female rats. Upon successful completion of these studies we will have determined the relative medical importance of cathinone stereoisomers, and developed the first specific medication for treating cathinone abuse.