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Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter.
Br J Pharmacol. 2013 Apr; 168(7):1750-7.BJ

Abstract

BACKGROUND AND PURPOSE

Bath salts is the street name for drug combinations that contain synthetic cathinone analogues, among them possibly mephedrone (MEPH) and certainly methylenedioxypyrovalerone (MDPV). In animal studies, cathinone and certain cathinone analogues release dopamine (DA), similar to the action of amphetamine (AMPH) and methamphetamine (METH). AMPH and METH act on the human DA transporter (hDAT); thus, we investigated MEPH and MDPV acting at hDAT.

EXPERIMENTAL APPROACH

We recorded electrical currents mediated by hDAT expressed in Xenopus laevis oocytes and exposed to: DA, METH, a known hDAT stimulant and DA releaser, MEPH, MDPV, MEPH + MDPV, or cocaine, a known hDAT inhibitor.

KEY RESULTS

DA, METH and MEPH induce an inward current (depolarizing) when the oocyte is held near the resting potential (-60 mV), therefore acting as excitatory hDAT substrates. Structurally analogous MDPV induces an outward (hyperpolarizing) current similar to cocaine, therefore acting as an inhibitory non-substrate blocker.

CONCLUSIONS AND IMPLICATIONS

Two components of bath salts, MEPH and MDPV, produce opposite effects at hDAT that are comparable with METH and cocaine, respectively. In our assay, MEPH is nearly as potent as METH; however, MDPV is much more potent than cocaine and its effect is longer lasting. When applied in combination, MEPH exhibits faster kinetics than MDPV, viz., the MEPH depolarizing current occurs seconds before the slower MDPV hyperpolarizing current. Bath salts containing MEPH (or a similar drug) and MDPV might then be expected initially to release DA and subsequently prevent its reuptake via hDAT. Such combined action possibly underlies some of the reported effects of bath salts abuse.

Authors+Show Affiliations

Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298, USA.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

23170765

Citation

Cameron, Krasnodara N., et al. "Bath Salts Components Mephedrone and Methylenedioxypyrovalerone (MDPV) Act Synergistically at the Human Dopamine Transporter." British Journal of Pharmacology, vol. 168, no. 7, 2013, pp. 1750-7.
Cameron KN, Kolanos R, Solis E, et al. Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. Br J Pharmacol. 2013;168(7):1750-7.
Cameron, K. N., Kolanos, R., Solis, E., Glennon, R. A., & De Felice, L. J. (2013). Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. British Journal of Pharmacology, 168(7), 1750-7. https://doi.org/10.1111/bph.12061
Cameron KN, et al. Bath Salts Components Mephedrone and Methylenedioxypyrovalerone (MDPV) Act Synergistically at the Human Dopamine Transporter. Br J Pharmacol. 2013;168(7):1750-7. PubMed PMID: 23170765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. AU - Cameron,Krasnodara N, AU - Kolanos,Renata, AU - Solis,Ernesto,Jr AU - Glennon,Richard A, AU - De Felice,Louis J, PY - 2012/07/10/received PY - 2012/10/20/revised PY - 2012/11/09/accepted PY - 2012/11/23/entrez PY - 2012/11/23/pubmed PY - 2013/12/16/medline SP - 1750 EP - 7 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 168 IS - 7 N2 - BACKGROUND AND PURPOSE: Bath salts is the street name for drug combinations that contain synthetic cathinone analogues, among them possibly mephedrone (MEPH) and certainly methylenedioxypyrovalerone (MDPV). In animal studies, cathinone and certain cathinone analogues release dopamine (DA), similar to the action of amphetamine (AMPH) and methamphetamine (METH). AMPH and METH act on the human DA transporter (hDAT); thus, we investigated MEPH and MDPV acting at hDAT. EXPERIMENTAL APPROACH: We recorded electrical currents mediated by hDAT expressed in Xenopus laevis oocytes and exposed to: DA, METH, a known hDAT stimulant and DA releaser, MEPH, MDPV, MEPH + MDPV, or cocaine, a known hDAT inhibitor. KEY RESULTS: DA, METH and MEPH induce an inward current (depolarizing) when the oocyte is held near the resting potential (-60 mV), therefore acting as excitatory hDAT substrates. Structurally analogous MDPV induces an outward (hyperpolarizing) current similar to cocaine, therefore acting as an inhibitory non-substrate blocker. CONCLUSIONS AND IMPLICATIONS: Two components of bath salts, MEPH and MDPV, produce opposite effects at hDAT that are comparable with METH and cocaine, respectively. In our assay, MEPH is nearly as potent as METH; however, MDPV is much more potent than cocaine and its effect is longer lasting. When applied in combination, MEPH exhibits faster kinetics than MDPV, viz., the MEPH depolarizing current occurs seconds before the slower MDPV hyperpolarizing current. Bath salts containing MEPH (or a similar drug) and MDPV might then be expected initially to release DA and subsequently prevent its reuptake via hDAT. Such combined action possibly underlies some of the reported effects of bath salts abuse. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/23170765/Bath_salts_components_mephedrone_and_methylenedioxypyrovalerone__MDPV__act_synergistically_at_the_human_dopamine_transporter_ L2 - https://doi.org/10.1111/bph.12061 DB - PRIME DP - Unbound Medicine ER -