Affiliation:
1. Department of Forensic Genetics and Forensic Toxicology National Board of Forensic Medicine Linköping Sweden
2. Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences Linköping University Linköping Sweden
3. Center for Forensic Science Advancement and Application, RTI International Research Triangle Park North Carolina USA
Abstract
AbstractMany new psychoactive substances (NPS) are stimulants, and information about their potency and abuse potential is often lacking. To start addressing this need, a method measuring the inhibition of the dopamine, serotonin, and norepinephrine transporters (DAT, SERT, and NET) by stimulant drugs was developed. The use of a proprietary fluorescent dye mixture and three cell lines (CHO‐K1, HEK 293, and MDCK), each expressing a single transporter, allowed for a semiautomated, one‐pot determination of inhibition in a 384‐well format. The method was validated using well characterized stimulants, including cocaine, amphetamine, 3,4‐methylenedioxymethamphetamine (MDMA), α‐PVP, and fluoxetine and performed similarly to other methods. Seven synthetic cathinones all showed highest potency for DAT inhibition, followed by NET and SERT. The rank potency for DAT inhibition IC50 (nM) was MPHP (4.53) > 4Cl‐α‐PVP (8.05) > 3F‐α‐PVP (12.7) > α‐PiHP (13.4) > N‐ethylpentylone (16.9) > N‐ethylhexedrone (44.5) > 4‐methylpentedrone (261). All but 4‐methylpentedrone were more potent than amphetamine (257) and cocaine (111). The DAT/SERT inhibition ratio for the cathinones was in the range from 5.02 for 4‐methylpentedrone to >3730 for α‐PiHP, compared to 1.64 for cocaine and >4030 for α‐PVP. All seven substances had inhibition profiles similar to those of potent stimulants with high abuse potential.
Subject
Spectroscopy,Pharmaceutical Science,Environmental Chemistry,Analytical Chemistry
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