Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter

作者：Cameron Krasnodara N; Kolanos Renata; Solis Ernesto Jr; Glennon Richard A; De Felice Louis J^*

来源：British Journal of Pharmacology, 2013, 168(7): 1750-1757.

DOI：10.1111/bph.12061

• bath salts
• synthetic cathinones
• dopamine transporter
• methamphetamine
• mephedrone (MEPH
• also 4-methylmethcathinone or MMC)
• methylenedioxypyrovalerone (MDPV)
• cocaine

Background and Purpose Bath salts is the street name for drug combinations that contain synthetic cathinone analogues, among them possibly mephedrone (MEPH) and certainly methylenedioxypyrovalerone (MDPV). In animal studies, cathinone and certain cathinone analogues release dopamine (DA), similar to the action of amphetamine (AMPH) and methamphetamine (METH). AMPH and METH act on the human DA transporter (hDAT); thus, we investigated MEPH and MDPV acting at hDAT. Experimental Approach We recorded electrical currents mediated by hDAT expressed in Xenopus laevis oocytes and exposed to: DA, METH, a known hDAT stimulant and DA releaser, MEPH, MDPV, MEPH+MDPV, or cocaine, a known hDAT inhibitor. Key Results DA, METH and MEPH induce an inward current (depolarizing) when the oocyte is held near the resting potential (60mV), therefore acting as excitatory hDAT substrates. Structurally analogous MDPV induces an outward (hyperpolarizing) current similar to cocaine, therefore acting as an inhibitory non-substrate blocker. Conclusions and Implications Two components of bath salts, MEPH and MDPV, produce opposite effects at hDAT that are comparable with METH and cocaine, respectively. In our assay, MEPH is nearly as potent as METH; however, MDPV is much more potent than cocaine and its effect is longer lasting. When applied in combination, MEPH exhibits faster kinetics than MDPV, viz., the MEPH depolarizing current occurs seconds before the slower MDPV hyperpolarizing current. Bath salts containing MEPH (or a similar drug) and MDPV might then be expected initially to release DA and subsequently prevent its reuptake via hDAT. Such combined action possibly underlies some of the reported effects of bath salts abuse.

• 出版日期2013-4