Methylone and Monoamine Transporters: Correlation with Toxicity
Chiharu Sogawa, Norio Sogawa, Kazumi Ohyama, Ruri Kikura-Hanajiri, Yukihiro Goda, Ichiro Sora, Shigeo Kitayama
Current Neuropharmacology March 1, 2011 DOI: 10.2174/157015911795017425 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | CHO cells expressing human dopamine, norepinephrine, serotonin, or GABA transporters |
| Interventions | Methylone methamphetamine |
| Topics | MDMA Serotonin |
| Keywords | Methamphetamine Monoaminergic Monoamine neurotransmitter Pharmacology Norepinephrine transporter Dopamine Endocrinology Biochemistry |
| Citations | 50 |
| Key findings | Methylone inhibits monoamine transporters with a rank order of NET > DAT > SERT and synergistically increases methamphetamine toxicity in cells expressing these transporters. |
Abstract
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.