Neurobiology of 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinovalerophenone (α-PVP)

• Nomenclature of synthetic cathinones.
• Mechanism of action of MDPV and α-PVP.
• Structure activity relationships for action as DAT reuptake inhibition.
• Metabolism of α-PVP analogs.
• Behavioral actions of MDPV and α-PVP.

Synthetic cathinones are analogs of cathinone or β-ketoamphetamine – the major psychostimulant component of the shrub Catha edulis or khat. Cathinone analogs – though not termed as such – have been known for >100 years, but confusing chemical nomenclature often made the topic difficult to appreciate. In addition, many of the early analogs were prepared as synthetic precursors for the development of various other agents, and relatively few were pharmacologically evaluated. Cathinone is a close structural relative of amphetamine. Today, certain cathinone derivatives, synthetic cathinones, are known to produce central stimulant actions and represent a “new” class of drugs of abuse. Depending upon the nature of their terminal amine, α substituent, and aryl substituents, they seem to produce their effects via release or reuptake of various neurotansmitters including dopamine norepinephreine and/or serotonin. Two of the newest and most prominent members of the class are MDPV and its parent α-PVP (“flakka”). Both have been encountered on their own and in what might be constituents of what has been termed by a variety of names including psychoactive “bath salts”. Here, we describe the nomenclature of synthetic cathinones, the mechanism(s) of action of MDPV and α-PVP, and their structure-activity relationships. In order to assist in forensic studies, and to identify novel substances requiring future pharmacological evaluation, the metabolism of these agents is also described. Finally, the preclinical behavioral actions of these two agents in a variety of behavioral assays, including rodent locomotor assays, self-administration studies, intracranial self-stimulation, conditioned place preference, and drug discrimination, is summarized. The results of these studies with MDPV and α-PVP are consistent with their acting as potent cocaine-like central stimulants with abuse liability.