Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of “bath salts,” produce opposite effects at the human dopamine transporter

• Published in: Psychopharmacology Vol. 227; no. 3; pp. 493 - 499
• Main Authors: Cameron, Krasnodara, Kolanos, Renata, Verkariya, Rakesh, De Felice, Louis, Glennon, Richard A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-06-2013; Springer; Springer Nature B.V
• Subjects: Animals; Benzodioxoles - chemistry; Benzodioxoles - pharmacology; Biomedical and Life Sciences; Biomedicine; Central Nervous System Stimulants - chemistry; Central Nervous System Stimulants - pharmacology; Designer Drugs - chemistry; Designer Drugs - pharmacology; Dopamine; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine Plasma Membrane Transport Proteins - metabolism; Dose-Response Relationship, Drug; Drug abuse; Humans; In Vitro Techniques; Membrane Potentials - drug effects; Mephedrone; Methamphetamine - analogs & derivatives; Methamphetamine - chemistry; Methamphetamine - pharmacology; Methcathinone; Molecular Structure; Neurosciences; Oocytes - metabolism; Original Investigation; Patch-Clamp Techniques; Pharmacology/Toxicology; Properties; Psychiatry; Psychopharmacology; Pyrrolidines - chemistry; Pyrrolidines - pharmacology; Structure-Activity Relationship; Synaptic Transmission - drug effects; Synthetic products; Transfection; Xenopus laevis; United States; Mephedrone; Drug abuse; Methcathinone; Methamphetamine; Synthetic cathinones; Dopamine transporter; Cocaine; Methylenedioxypyrovalerone; hDAT
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-2967-2

Rationale
Psychoactive “bath salts” represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated.
Materials and methods
Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in
Xenopus
oocytes.
Results
Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine.
Conclusions
Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine.