Interaction Profiles of Central Nervous System Active Drugs at Human Organic Cation Transporters 1-3 and Human Plasma Membrane Monoamine Transporter.
International journal of molecular sciences November 30, 2021 Thomas J F Angenoorth, Stevan Stankovic, Marco Niello et al. 18 citations
Many psychoactive compounds primarily interact with high-affinity monoamine transporters, but their interactions with low-affinity, high-capacity transporters like human organic cation transporters (hOCTs) and the plasma membrane monoamine transporter (hPMAT) are understudied. Using radiotracer-based uptake inhibition assays in HEK293 cells, 17 psychoactive substances were tested. Most compounds inhibited hOCT1 and hOCT2 in the low micromolar range, while few affected hOCT3 or hPMAT. Methylphenidate and ketamine selectively inhibited hOCT1 or hOCT2, respectively, and MDMA potently inhibited hOCT1, hOCT2, and hPMAT. Enantiospecific differences were observed for R- and S-α-PVP and R- and S-citalopram. These findings highlight the importance of studying drug interactions with hOCTs and hPMAT for regulating monoamine concentrations and xenobiotic clearance.