amphetamines), while circumventing current legal restrictions on controlled substances due to their unique chemical structures ( Baumann et al., 2014). NPS are designed to imitate the actions of known drugs of abuse (e.g. Novel synthetic drugs of abuse, more formally known as new psychoactive substances (NPS), are appearing at a rapid pace on recreational drug markets worldwide ( Welter-Luedeke and Maurer, 2016). 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 addiction. Each FPM evoked concentration-dependent release of monoamines from rat brain synaptosomes. Experiments directed at identifying transporter-mediated reverse transport revealed that FPM isomers induce efflux via DAT, NET and SERT in HEK293 cells, and this effect is augmented by the Na +/H + ionophore monensin.
We found that 2-, 3- and 4-FPM inhibit uptake mediated by DAT and NET in HEK293 cells with potencies comparable to cocaine (IC 50 values 80 µM). 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). Phenmetrazine is known to elevate extracellular monoamine concentrations by an amphetamine-like mechanism. 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. 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.
NPS are compounds that target various receptors and transporters in the central nervous system to achieve their psychoactive effects. A variety of new psychoactive substances (NPS) are appearing in recreational drug markets worldwide.
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