MDPV (Methylenedioxypyrovalerone)

MDPV is a psychostimulant substance, classified under the phenethylamine and β- keto-amphetamine families. Its effects have been compared to those of cocaine and amphetamine, causing effects that include euphoria and increased alertness. MDPV is a notably more potent psychostimulant than cocaine, as the threshold dose tha causes hyperlocomotion in rats is 0.3mg/kg, which contrast with that for cocaine (10mg/kg) (Baumann et al., 2013).

Due to its potency, MDPV in highly dangerous, making it the most commonly found cathinone in blood and urine of patients admitted to the emergency room in the United States. In this sense, it has been reported to cause agitation, psychosis, tachycardia, and even death (Borek and Holstege, 2012; Spiller et al, 2011).

 

Mechanism of action of MDPV

MDPV is a catecholamine transporter blocker, mainly on DAT, thus eliciting the accumulation of dopamine and norepinephrine in the synaptic cleft. Unlike most phenethylamines, it does not act as substrate, which keeps it from entering the terminal and causing massive neurotransmitter release through reverse transport.

This mechanism of action is shared by the alkaloid cocaine and few amphetamine derivatives, bupropion (cathinone family) and methylphenidate being the most widely known examples. Nonetheless, MDPV is 10-fold more potent than cocaine in its ability to increase extracellular dopamine, as the lowest effective dose of MDPV is 0.1mg/kg, compared with 1.0 mg/kg for cocaine (Baumann et al., 2013). Furthermore, it is significantly more efficacious, resulting in a higher activity peak in hyperlocomotion assays.

 

Pharmacokinetics of MDPV

To date, information on this matter is scarce. It is known that MDPV shows linear kinetics, with a relatively short half-life (75 minutes) (Anizan et al., 2014; Novellas et al., 2015). Furthermore, both studies described that MDPV undergoes phase I metabolism, consisting of a demethylation of the methylendioxy group to form the corresponding diol (3,4-catechol-PV), followed by a O-methylation, generating the hydroxylated metabolite (4-OH-3-MeO-PV or 3-OH-4-MeO-PV); these metabolites can be subsequently hydroxylated on the aromatic ring, forming 4,?-OH-3-MeO-PV or 3,?-OH-4-MeO-PV (the postition at which hydroxylation takes place has not been determined).

 

Neurotoxicity of MDPV

There are nearly no reports on MDPV-induced neurotoxicity. Ádam et al. (2014) demonstrated that MDPV does not affect apoptosis in the adult rat brain. Furthermore, a recent study showed that MDPV attenuates methamphetamine- induced signs of neurotoxicity (Anneken et al., 2015). This phenomenon could be due to its unique nature as a catecholamine transporter blocker, rather than a releaser, which would block extracellular dopamine from being internalized in the terminal, where its subsequent oxidation would generate toxic reactive oxygen species (ROS). This is backed by additional findings showing that MDPV dose-

dependently blocks methamphetamine-induced dopamine release (Simmler et al., 2013). Taken together, it can be hypothesized that MDPV possesses limited neurotoxic potential.