The psychostimulant (±)-cis-4,4-dimethylaminorex (4,4-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters.
(±)-cis-4,4-Dimethylaminorex (4,4-DMAR) is a new psychoactive substance (NPS) that has been associated with 31 fatalities and other adverse events in Europe between June 2013 and February 2014. We used in vitro uptake inhibition and transporter release assays to determine the effects of 4,4-DMAR on human high-affinity transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). In addition, we assessed its binding affinities to monoamine receptors and transporters. Furthermore, we investigated the interaction of 4,4-DMAR with the vesicular monoamine transporter 2 (VMAT2) in rat phaeochromocytoma (PC12) cells and synaptic vesicles prepared from human striatum. 4,4-DMAR inhibited uptake mediated by human DAT, NET or SERT, respectively in the low micromolar range (IC