The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue.
Michael H Baumann, Mario A Ayestas, John S. Partilla, Jacqueline R Sink, Alexander T. Shulgin, Paul F. Daley, Simon D. Brandt, Richard B Rothman, Arnold E. Ruoho, Nicholas V. Cozzi
Neuropsychopharmacology December 14, 2011 DOI: 10.1038/npp.2011.304 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro and in vivo preclinical study Peer reviewed |
|---|---|
| Population | Rats (synaptosomes and nucleus accumbens microdialysis) |
| Interventions | Mephedrone Methylone MDMA Methamphetamine |
| Dose | 0.3 and 1.0 mg/kg i.v. (mephedrone or methylone); 3.0 and 10.0 mg/kg s.c. (mephedrone or methylone, 3 doses); 2.5 and 7.5 mg/kg s.c. (MDMA, 3 doses) |
| Topics | Serotonin |
| Keywords | Nucleus accumbens Synaptosomes Animals Rats, sprague-dawley Tritium Dopamine Methamphetamine N-methyl-3,4-methylenedioxyamphetamine 1-methyl-4-phenylpyridinium Membrane transport proteins Hallucinogens Microdialysis Analysis of variance Locomotion Dose-response relationship, drug Electrochemistry Time factors Male In vitro techniques |
| Key points | Mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters with transmitter-releasing activity comparable to MDMA, and they increase extracellular dopamine and serotonin in the nucleus accumbens. Unlike MDMA, repeated treatment did not persistently deplete cortical or striatal serotonin, though the authors suggest dopaminergic effects may contribute to addictive potential, a hypothesis they say awaits confirmation. |
Abstract
The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study.
Comparable studies
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| Study | Year | Design | Participants |
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| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
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- Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants Frontiers in Neuroscience April 19, 2016
- Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine Life Science July 24, 2013
- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Designer drugs 2015: assessment and management Addiction Science & Clinical Practice March 11, 2015
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Cites 12
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- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
- Methylone and Monoamine Transporters: Correlation with Toxicity Current Neuropharmacology March 1, 2011
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