4.7 Article

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive 'Bath Salts' Products

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NEUROPSYCHOPHARMACOLOGY
卷 38, 期 4, 页码 552-562

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NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2012.204

关键词

designer drug; dopamine; cathinone; monoamine transporter; uptake blocker

资金

  1. Austrian Science Fund/FWF [SFB3506]
  2. Austrian Science Fund (FWF) [F 3506] Funding Source: researchfish

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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 [H-3]dopamine (IC50=4.1 nM) and [H-3]norepinephrine (IC50=26 nM) with high potency but has weak effects on uptake of [H-3]serotonin (IC50=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. Neuropsychopharmacology (2013) 38, 552-562; doi:10.1038/npp.2012.204; published online 17 October 2012

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