TY - JOUR T1 - Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products. AU - Baumann,Michael H, AU - Partilla,John S, AU - Lehner,Kurt R, AU - Thorndike,Eric B, AU - Hoffman,Alexander F, AU - Holy,Marion, AU - Rothman,Richard B, AU - Goldberg,Steven R, AU - Lupica,Carl R, AU - Sitte,Harald H, AU - Brandt,Simon D, AU - Tella,Srihari R, AU - Cozzi,Nicholas V, AU - Schindler,Charles W, Y1 - 2012/10/17/ PY - 2012/10/18/entrez PY - 2012/10/18/pubmed PY - 2013/10/30/medline SP - 552 EP - 62 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 38 IS - 4 N2 - The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [(3)H]dopamine (IC(50)=4.1 nM) and [(3)H]norepinephrine (IC(50)=26 nM) with high potency but has weak effects on uptake of [(3)H]serotonin (IC(50)=3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/23072836/Powerful_cocaine_like_actions_of_34_methylenedioxypyrovalerone__MDPV__a_principal_constituent_of_psychoactive_'bath_salts'_products_ L2 - http://dx.doi.org/10.1038/npp.2012.204 DB - PRIME DP - Unbound Medicine ER -