Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):58-62. doi: 10.2174/157015911795017425.
Methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propane-1-one) is a synthetic hallucinogenic amphetamine analog, like MDMA (3,4-methylenedioxy- methamphetamine), considered to act on monoaminergic systems. However, the psychopharmacological profile of its cytotoxicity as a consequence of monoaminergic deficits remains unclear. We examined here the effects of methylone on the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), using a heterologous expression system in CHO cells, in association with its cytotoxicity. Methylone inhibited the activities of DAT, NET, and SERT, but not GABA transporter-1 (GAT1), in a concentration-dependent fashion with a rank order of NET > DAT > SERT. Methylone was less effective at inhibiting DAT and NET, but more effective against SERT, than was methamphetamine. Methylone alone was not toxic to cells except at high concentrations, but in combination with methamphetamine had a synergistic effect in CHO cells expressing the monoamine transporters but not in control CHO cells or cells expressing GAT1. The ability of methylone to inhibit monoamine transporter function, probably by acting as a transportable substrate, underlies the synergistic effect of methylone and methamphetamine.
3,4-亚甲二氧基甲基苯丙胺（MDMA）是一种合成致幻苯丙胺类似物，类似于 3,4-亚甲二氧基苯丙胺（MDA），被认为作用于单胺能系统。然而，其作为单胺能缺陷的细胞毒性的精神药理学特征仍不清楚。我们在此使用 CHO 细胞的异源表达系统，结合其细胞毒性，研究了 3,4-亚甲二氧基甲基苯丙胺对多巴胺（DAT）、去甲肾上腺素（NET）和 5-羟色胺（SERT）转运体的影响。3,4-亚甲二氧基甲基苯丙胺以浓度依赖的方式抑制 DAT、NET 和 SERT 的活性，但对 GABA 转运体-1（GAT1）没有抑制作用，其抑制活性的顺序为 NET>DAT>SERT。3,4-亚甲二氧基甲基苯丙胺对 DAT 和 NET 的抑制作用弱于 3,4-亚甲二氧基苯丙胺，但对 SERT 的抑制作用强于 3,4-亚甲二氧基苯丙胺。3,4-亚甲二氧基甲基苯丙胺单独使用时除高浓度外对细胞没有毒性，但与 3,4-亚甲二氧基苯丙胺联合使用时，在表达单胺转运体的 CHO 细胞中具有协同作用，但在对照 CHO 细胞或表达 GAT1 的细胞中没有协同作用。3,4-亚甲二氧基甲基苯丙胺抑制单胺转运体功能的能力，可能是通过作为可转运的底物，是 3,4-亚甲二氧基甲基苯丙胺和 3,4-亚甲二氧基苯丙胺协同作用的基础。
