Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of “bath salts,” produce opposite effects at the human dopamine transporter

Rationale Psychoactive “bath salts” represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cat...

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Published in:	Psychopharmacology Vol. 227; no. 3; pp. 493 - 499
Main Authors:	Cameron, Krasnodara, Kolanos, Renata, Verkariya, Rakesh, De Felice, Louis, Glennon, Richard A.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer-Verlag 01-06-2013 Springer Springer Nature B.V
Subjects:	Animals Benzodioxoles - chemistry Benzodioxoles - pharmacology Biomedical and Life Sciences Biomedicine Central Nervous System Stimulants - chemistry Central Nervous System Stimulants - pharmacology Designer Drugs - chemistry Designer Drugs - pharmacology Dopamine Dopamine Plasma Membrane Transport Proteins - genetics Dopamine Plasma Membrane Transport Proteins - metabolism Dose-Response Relationship, Drug Drug abuse Humans In Vitro Techniques Membrane Potentials - drug effects Mephedrone Methamphetamine - analogs & derivatives Methamphetamine - chemistry Methamphetamine - pharmacology Methcathinone Molecular Structure Neurosciences Oocytes - metabolism Original Investigation Patch-Clamp Techniques Pharmacology/Toxicology Properties Psychiatry Psychopharmacology Pyrrolidines - chemistry Pyrrolidines - pharmacology Structure-Activity Relationship Synaptic Transmission - drug effects Synthetic products Transfection Xenopus laevis United States Mephedrone Drug abuse Methcathinone Methamphetamine Synthetic cathinones Dopamine transporter Cocaine Methylenedioxypyrovalerone hDAT
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Abstract	Rationale Psychoactive “bath salts” represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. Materials and methods Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. Results Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. Conclusions Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine.
AbstractList	Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine. Rationale Psychoactive “bath salts” represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. Materials and methods Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. Results Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. Conclusions Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine. Rationale: Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. Materials and methods: Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. Results: Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. Conclusions: Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine. Rationale Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. Materials and methods Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. Results Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. Conclusions Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine. Keywords Synthetic cathinones * Cocaine * Dopamine transporter * hDAT * Mephedrone * Methamphetamine * Methcathinone * Methylenedioxypyrovalerone * Drug abuse Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine.[PUBLICATION ABSTRACT]
Audience	Academic
Author	Verkariya, Rakesh De Felice, Louis Cameron, Krasnodara Glennon, Richard A. Kolanos, Renata
AuthorAffiliation	2 Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, 23298 USA 1 Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, 23298 USA
AuthorAffiliation_xml	– name: 1 Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, 23298 USA – name: 2 Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, 23298 USA
Author_xml	– sequence: 1 givenname: Krasnodara surname: Cameron fullname: Cameron, Krasnodara organization: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University – sequence: 2 givenname: Renata surname: Kolanos fullname: Kolanos, Renata organization: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University – sequence: 3 givenname: Rakesh surname: Verkariya fullname: Verkariya, Rakesh organization: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University – sequence: 4 givenname: Louis surname: De Felice fullname: De Felice, Louis email: ljdefelice@vcu.edu organization: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University – sequence: 5 givenname: Richard A. surname: Glennon fullname: Glennon, Richard A. email: glennon@vcu.edu organization: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23371489$$D View this record in MEDLINE/PubMed
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Snippet	Rationale Psychoactive “bath salts” represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients... Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath... Rationale Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients... Rationale: Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients...
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SubjectTerms	Animals Benzodioxoles - chemistry Benzodioxoles - pharmacology Biomedical and Life Sciences Biomedicine Central Nervous System Stimulants - chemistry Central Nervous System Stimulants - pharmacology Designer Drugs - chemistry Designer Drugs - pharmacology Dopamine Dopamine Plasma Membrane Transport Proteins - genetics Dopamine Plasma Membrane Transport Proteins - metabolism Dose-Response Relationship, Drug Drug abuse Humans In Vitro Techniques Membrane Potentials - drug effects Mephedrone Methamphetamine - analogs & derivatives Methamphetamine - chemistry Methamphetamine - pharmacology Methcathinone Molecular Structure Neurosciences Oocytes - metabolism Original Investigation Patch-Clamp Techniques Pharmacology/Toxicology Properties Psychiatry Psychopharmacology Pyrrolidines - chemistry Pyrrolidines - pharmacology Structure-Activity Relationship Synaptic Transmission - drug effects Synthetic products Transfection Xenopus laevis
Title	Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of “bath salts,” produce opposite effects at the human dopamine transporter
URI	https://link.springer.com/article/10.1007/s00213-013-2967-2 https://www.ncbi.nlm.nih.gov/pubmed/23371489 https://www.proquest.com/docview/1354349806 https://search.proquest.com/docview/1356936602 https://pubmed.ncbi.nlm.nih.gov/PMC3881434
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