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A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Methylone and monoamine transporters: correlation with toxicity
Chiharu Sogawa1, Norio Sogawa, Kazumi Ohyama
1Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Current Neuropharmacology
|September 3, 2011
Summary
Methylone, a synthetic amphetamine, inhibits dopamine, norepinephrine, and serotonin transporters. It synergistically increases methamphetamine toxicity in cells expressing these transporters, likely by acting as a substrate.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methylone is a synthetic amphetamine analog with effects on monoaminergic systems.
- The cytotoxicity of methylone, particularly concerning monoaminergic deficits, is not fully understood.
Purpose of the Study:
- To investigate the effects of methylone on dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters.
- To assess the cytotoxicity of methylone, alone and in combination with methamphetamine, in cells expressing monoamine transporters.
Main Methods:
- Utilized a heterologous expression system in Chinese hamster ovary (CHO) cells.
- Assessed transporter inhibition by methylone and methamphetamine.
- Evaluated cytotoxicity in control CHO cells, cells expressing monoamine transporters, and cells expressing GABA transporter-1 (GAT1).
Main Results:
- Methylone inhibited DAT, NET, and SERT activity in a concentration-dependent manner (NET > DAT > SERT).
- Methylone showed greater potency against SERT inhibition compared to methamphetamine.
- Methylone potentiated methamphetamine-induced cytotoxicity synergistically in cells expressing monoamine transporters, but not in control cells or GAT1-expressing cells.
Conclusions:
- Methylone's inhibition of monoamine transporter function contributes to its psychopharmacological profile.
- Methylone likely acts as a transportable substrate, enhancing the synergistic toxicity observed with methamphetamine.
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