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Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products.
Neuropsychopharmacology. 2013 Mar; 38(4):552-62.N

Abstract

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.

Authors+Show Affiliations

Medicinal Chemistry Section of the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. mbaumann@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23072836

Citation

Baumann, Michael H., et al. "Powerful Cocaine-like Actions of 3,4-methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive 'bath Salts' Products." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 38, no. 4, 2013, pp. 552-62.
Baumann MH, Partilla JS, Lehner KR, et al. Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products. Neuropsychopharmacology. 2013;38(4):552-62.
Baumann, M. H., Partilla, J. S., Lehner, K. R., Thorndike, E. B., Hoffman, A. F., Holy, M., Rothman, R. B., Goldberg, S. R., Lupica, C. R., Sitte, H. H., Brandt, S. D., Tella, S. R., Cozzi, N. V., & Schindler, C. W. (2013). Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 38(4), 552-62. https://doi.org/10.1038/npp.2012.204
Baumann MH, et al. Powerful Cocaine-like Actions of 3,4-methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive 'bath Salts' Products. Neuropsychopharmacology. 2013;38(4):552-62. PubMed PMID: 23072836.
* Article titles in AMA citation format should be in sentence-case
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 -