Electrophysiological Actions of Synthetic Cathinones on Monoamine Transporters

Products containing psychoactive synthetic cathinones, such as mephedrone and 3,4-methylenedioxypyrovalerone (MDPV) are prevalent in our society. Synthetic cathinones are structurally similar to methamphetamine, and numerous synthetics have biological activity at dopamine, serotonin, and norepinephrine transporters. Importantly, monoamine transporters co-transport sodium ions along with their substrate, and movement of substrates and ions through the transporter can generate measurable ionic currents. Here we review how electrophysiological information has enabled us to determine how synthetic cathinones affect transporter-mediated currents in cells that express these transporters. Specifically, drugs that act as transporter substrates induce inward depolarizing currents when cells are held near their resting membrane potential, whereas drugs that act as transporter blockers induce apparent outward currents by blocking an inherent inward leak current. We have employed the two-electrode voltage-clamp technique in Xenopus laevis oocytes overexpressing monoamine transporters to determine whether synthetic cathinones found in the so-called bath salts products behave as blockers or substrates. We also examined the structure-activity relationships for synthetic cathinone analogs related to the widely abused compound MDPV, a common constituent in "bath salts" possessing potent actions at the dopamine transporter.