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dc.contributor.authorMayer, Felix P.
dc.contributor.authorBurchardt, Nadine V.
dc.contributor.authorDecker, Ann M.
dc.contributor.authorPartilla, John S.
dc.contributor.authorLi, Yang
dc.contributor.authorMcLaughlin, Gavin
dc.contributor.authorKavanagh, Pierce V.
dc.contributor.authorSandtner, Walter
dc.contributor.authorBlough, Bruce E.
dc.contributor.authorBrandt, Simon D.
dc.contributor.authorBaumann, Michael H.
dc.contributor.authorSitte, Harald H.
dc.identifier.citationMayer, F.P., Burchardt, N., Decker, A.M., Partilla, J.S., Li, Y., McLaughlin, G., Kavanagh, P.V., Sandtner, W., Blough, B.E., Brandt, S.D., Baumann, M.H., Sitte, H.H. (2017). Neuropharmacology. 134 (2018): 149-157.
dc.identifier.otherArticles - Life and Physical Sciences AITen_US
dc.description.abstractA variety of new psychoactive substances (NPS) are appearing in recreational drug markets worldwide. NPS are compounds that target various receptors and transporters in the central nervous system to achieve their psychoactive effects. Chemical modifications of existing drugs can generate NPS that are not controlled by current legislation, thereby providing legal alternatives to controlled substances such as cocaine or amphetamine. Recently, 3-fluorophenmetrazine (3-FPM), a derivative of the anorectic compound phenmetrazine, appeared on the recreational drug market and adverse clinical effects have been reported. Phenmetrazine is known to elevate extracellular monoamine concentrations by an amphetamine-like mechanism. Here we tested 3-FPM and its positional isomers, 2-FPM and 4-FPM, for their abilities to interact with plasma membrane monoamine transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). We found that 2-, 3- and 4-FPM inhibit uptake mediated by DAT and NET in HEK293 cells with potencies comparable to cocaine (IC50 values < 2.5 mM), but display less potent effects at SERT (IC50 values >80 mM). Experiments directed at identifying transportermediated reverse transport revealed that FPM isomers induce efflux via DAT, NET and SERT in HEK293 cells, and this effect is augmented by the Naþ/Hþ ionophore monensin. Each FPM evoked concentration-dependent release of monoamines from rat brain synaptosomes. Hence, this study reports for the first time the mode of action for 2-, 3- and 4-FPM and identifies these NPS as monoamine releasers with marked potency at catecholamine transporters implicated in abuse and addictionen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland*
dc.subjectNew psychoactive substancesen_US
dc.subjectLegal highen_US
dc.subjectMonoamine transporteren_US
dc.titleFluorinated phenmetrazine “legal highs” act as substrates for high-affinity monoamine transporters of the SLC6 family.en_US
dc.identifier.doidoi: 10.1016/j.neuropharm.2017.10.006
dc.rights.accessOpen Accessen_US
dc.subject.departmentFaculty of Science and Healthen_US

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