title: A combined approach using transporter-flux assays and mass spectrometry to examine psychostimulant street drugs of unknown content.
abstract: The illicit consumption of psychoactive compounds may cause short and long-term health problems and addiction. This is also true for amphetamines and cocaine, which target monoamine transporters. In the recent past, an increasing number of new compounds with amphetamine-like structure such as mephedrone or 3,4-methylenedioxypyrovalerone (MDPV) entered the market of illicit drugs. Subtle structural changes circumvent legal restrictions placed on the parent compound. These novel drugs are effectively marketed "designer drugs" (also called "research chemicals") without any knowledge of the underlying pharmacology, the potential harm or a registration of the manufacturing process. Accordingly new entrants and their byproducts are identified postmarketing by chemical analysis and their pharmacological properties inferred by comparison to compounds of known structure. However, such a heuristic approach fails, if the structures diverge substantially from a known derivative. In addition, the understanding of structure-activity relations is too rudimentary to predict detailed pharmacological activity. Here, we tested a combined approach by examining the composition of street drugs using mass spectrometry and by assessing the functional activity of their constituents at the neuronal transporters for dopamine, serotonin, and norepinephrine. We show that this approach is superior to mere chemical analysis in recognizing novel and potentially harmful street drugs.
authors: Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Waehringer Strasse 13a, A-1090 Vienna, Austria.
authors: Rudolf
authors: R
authors: Rosenauer
authors: Anton
authors: A
authors: Luf
authors: Marion
authors: M
authors: Holy
authors: Michael
authors: M
authors: Freissmuth
authors: Rainer
authors: R
authors: Schmid
authors: Harald H
authors: HH
authors: Sitte
mesh_terms: D000697:Central Nervous System Stimulants / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015198:Designer Drugs / Q000032:analysis* / Q000737:chemistry; D050485:GABA Plasma Membrane Transport Proteins / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D013287:Illicit Drugs / Q000032:analysis* / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D011619:Psychotropic Drugs / Q000032:analysis* / Q000737:chemistry; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects; D015813:Substance Abuse Detection / Q000379:methods*; D050493:Vesicular Monoamine Transport Proteins / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D015198:Designer Drugs; D050485:GABA Plasma Membrane Transport Proteins; D013287:Illicit Drugs; D011619:Psychotropic Drugs; C493413:SLC6A1 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins