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"Deconstruction" of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter.
ACS Chem Neurosci. 2013 Dec 18; 4(12):1524-9.AC

Abstract

Synthetic cathinones, β-keto analogues of amphetamine (or, more correctly, of phenylalkylamines), represent a new and growing class of abused substances. Several such analogues have been demonstrated to act as dopamine (DA) releasing agents. Methylenedioxypyrovalerone (MDPV) was the first synthetic cathinone shown to act as a cocaine-like DA reuptake inhibitor. MDPV and seven deconstructed analogues were examined to determine which of MDPV's structural features account(s) for uptake inhibition. In voltage-clamped (-60 mV) Xenopus oocytes transfected with the human DA transporter (hDAT), all analogues elicited inhibitor-like behavior shown as hDAT-mediated outward currents. Using hDAT-expressing mammalian cells we determined the affinities of MDPV and its analogues to inhibit uptake of [3H]DA by hDAT that varied over a broad range (IC50 values ca. 135 to >25,000 nM). The methylenedioxy group of MDPV made a minimal contribution to affinity, the carbonyl group and a tertiary amine are more important, and the extended α-alkyl group seems most important. Either a tertiary amine, or the extended α-alkyl group (but not both), are required for the potent nature of MDPV as an hDAT inhibitor.

Authors+Show Affiliations

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University , Richmond, Virginia 23298, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24116392

Citation

Kolanos, Renata, et al. ""Deconstruction" of the Abused Synthetic Cathinone Methylenedioxypyrovalerone (MDPV) and an Examination of Effects at the Human Dopamine Transporter." ACS Chemical Neuroscience, vol. 4, no. 12, 2013, pp. 1524-9.
Kolanos R, Solis E, Sakloth F, et al. "Deconstruction" of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter. ACS Chem Neurosci. 2013;4(12):1524-9.
Kolanos, R., Solis, E., Sakloth, F., De Felice, L. J., & Glennon, R. A. (2013). "Deconstruction" of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter. ACS Chemical Neuroscience, 4(12), 1524-9. https://doi.org/10.1021/cn4001236
Kolanos R, et al. "Deconstruction" of the Abused Synthetic Cathinone Methylenedioxypyrovalerone (MDPV) and an Examination of Effects at the Human Dopamine Transporter. ACS Chem Neurosci. 2013 Dec 18;4(12):1524-9. PubMed PMID: 24116392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - "Deconstruction" of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter. AU - Kolanos,Renata, AU - Solis,Ernesto,Jr AU - Sakloth,Farhana, AU - De Felice,Louis J, AU - Glennon,Richard A, Y1 - 2013/10/31/ PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2014/8/22/medline SP - 1524 EP - 9 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 4 IS - 12 N2 - Synthetic cathinones, β-keto analogues of amphetamine (or, more correctly, of phenylalkylamines), represent a new and growing class of abused substances. Several such analogues have been demonstrated to act as dopamine (DA) releasing agents. Methylenedioxypyrovalerone (MDPV) was the first synthetic cathinone shown to act as a cocaine-like DA reuptake inhibitor. MDPV and seven deconstructed analogues were examined to determine which of MDPV's structural features account(s) for uptake inhibition. In voltage-clamped (-60 mV) Xenopus oocytes transfected with the human DA transporter (hDAT), all analogues elicited inhibitor-like behavior shown as hDAT-mediated outward currents. Using hDAT-expressing mammalian cells we determined the affinities of MDPV and its analogues to inhibit uptake of [3H]DA by hDAT that varied over a broad range (IC50 values ca. 135 to >25,000 nM). The methylenedioxy group of MDPV made a minimal contribution to affinity, the carbonyl group and a tertiary amine are more important, and the extended α-alkyl group seems most important. Either a tertiary amine, or the extended α-alkyl group (but not both), are required for the potent nature of MDPV as an hDAT inhibitor. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/24116392/"Deconstruction"_of_the_abused_synthetic_cathinone_methylenedioxypyrovalerone__MDPV__and_an_examination_of_effects_at_the_human_dopamine_transporter_ L2 - https://doi.org/10.1021/cn4001236 DB - PRIME DP - Unbound Medicine ER -