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Current Neuropharmacology
ISSN (Print): 1570-159X
ISSN (Online): 1875-6190
DOI: 10.2174/157015911795017425

Methylone and Monoamine Transporters: Correlation with Toxicity

Author(s): Chiharu Sogawa, Norio Sogawa, Kazumi Ohyama, Ruri Kikura-Hanajiri, Yukihiro Goda, Ichiro Sora and Shigeo Kitayama
Pages 58-62 (5)
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.
Methylone, neurotransmitter transporter, uptake, cocaine, methamphetamine, MDMA, Cytotoxicity, monoaminergic Systems, CHO cells, Dopamine (DAT), norpinephrine (NET)
Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata 2-5-1, Okayama 700-8525, Japan.