Mephedrone and methylone, two stimulants commonly found in designer drugs such as “bath salts,” act on the brain much like methylenedioxymethamphetamine (MDMA, Ecstasy). According to recent studies, the two may be addictive, but may not have the same propensity for causing toxicity as MDMA.
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Dr. Michael Baumann of NIDA’s Intramural Research Program and researchers at several centers collaborated to pin down the drugs’ pharmacological and behavioral effects. The researchers sampled rats’ extracellular brain fluid while the animals moved about after being dosed with one of the three stimulants or saline. Assays of the fluid revealed that all the drugs elevated extracellular concentrations of the neurotransmitters dopamine and serotonin, as shown by comparison with levels in the animals given saline. For all three drugs, the impact on serotonin was greater than that on dopamine (see Figure 1A and 1B).
Analysis of rats’ brain tissue revealed an underlying mechanism for the heightened neurotransmitter presence: All three drugs caused transporters in cellular membranes to release dopamine and serotonin into the extracellular space. This effect reverses the normal activity of the transporters, which is to draw the neurotransmitters out of the extracellular space.
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The fact that the three drugs produce similar pharmacologic effects is consistent with their similar chemical structures (see Figure 2). However, the researchers also found important differences between the drugs.
Whereas repeated high doses of MDMA markedly reduced serotonin concentrations in the cortex and striatum, the researchers did not see this effect with mephedrone or methylone. Moreover, although rats given acute doses of all three drugs exhibited locomotor stimulation and hyperthermia, repeated high doses of the drugs produced different behavioral responses. Specifically, instead of the flattened body posture and forepaw treading seen with MDMA, mephedrone and methylone induced rearing behavior.
Dr. Baumann and colleagues note that much research has shown that drugs which increase extracellular dopamine—as do all the drugs they tested—have high potential for addiction. They speculate that the differences in rats’ serotonin and behavioral responses to the drugs are linked, and may indicate that mephedrone and methylone have less toxic potential than MDMA. However, they emphasize that this hypothesis needs to be tested.
This study was supported by NIH grants DA017675 and DA027191.
Baumann, M.H., et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37(5):1192–1203, 2012. Full Text
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National Institute on Drug Abuse. Stimulants in “Bath Salts” Produce Effects Similar to MDMA Retrieved from http://www.drugabuse.gov/news-events/nida-notes/2013/08/stimulants-in-bath-salts-produce-effects-similar-to-mdma