Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Br J Pharmacol. 2013 Apr;168(7):1750-7. doi: 10.1111/bph.12061.
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.
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.
DA, METH and MEPH induce an inward current (depolarizing) when the oocyte is held near the resting potential (-60 mV), 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.
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.
浴盐是一种包含合成苯丙胺类似物的毒品混合物的俗称，其中可能有甲卡西酮（MEPH），肯定有 3,4-亚甲基二氧吡咯戊酮（MDPV）。在动物研究中，苯丙胺和某些苯丙胺类似物会释放多巴胺（DA），这与安非他命（AMPH）和甲基苯丙胺（METH）的作用类似。AMPH 和 METH 作用于人类多巴胺转运蛋白（hDAT）；因此，我们研究了作用于 hDAT 的 MEPH 和 MDPV。
我们记录了在非洲爪蟾卵母细胞中表达的 hDAT 介导的电流，并将其暴露于以下物质：DA、METH，一种已知的 hDAT 兴奋剂和 DA 释放剂，MEPH、MDPV、MEPH+MDPV 或可卡因，一种已知的 hDAT 抑制剂。
当卵母细胞被保持在静息电位（-60 mV）附近时，DA、METH 和 MEPH 会诱导内向电流（去极化），因此它们作为兴奋性 hDAT 底物。结构类似的 MDPV 会诱导类似可卡因的外向（超极化）电流，因此作为一种抑制性非底物阻滞剂。
浴盐的两种成分，MEPH 和 MDPV，在 hDAT 上产生与 METH 和可卡因分别相当的相反作用。在我们的测定中，MEPH 的效力几乎与 METH 相当；然而，MDPV 比可卡因更有效力，且其作用持续时间更长。当联合使用时，MEPH 比 MDPV 表现出更快的动力学，即 MEPH 的去极化电流在较慢的 MDPV 超极化电流之前几秒钟发生。含有 MEPH（或类似药物）和 MDPV 的浴盐可能最初会释放 DA，随后通过 hDAT 阻止其再摄取。这种联合作用可能是一些报道的浴盐滥用效应的基础。
