Methylone and Monoamine Transporters: Correlation with Toxicity

• Published in: Current neuropharmacology Vol. 9; no. 1; pp. 58 - 62
• Main Authors: Sogawa, Chiharu, Sogawa, Norio, Ohyama, Kazumi, Kikura-Hanajiri, Ruri, Goda, Yukihiro, Sora, Ichiro, Kitayama, Shigeo
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.03.2011
• Subjects: neurotransmitter transporter; Methylone; cocaine; methamphetamine; uptake; MDMA
• ISSN: 1570-159X; 1875-6190
• 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 concentrationdependent 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.