Karolina Elzbieta Kolaczynska, PhD candidate
University Hospital Basel, University of Basel
In vitro pharmacological characterization of 3,4-methylenedioxyamphetamine and amphetamine analogs.
To pharmacologically profile psychedelic designer drugs, 3,4-methylenedioxyamphetamine and amphetamine analogs at human monoamine uptake transporters and receptors.
HEK293 cells transfected with monoamine transporters (DAT, SERT, NET) were treated with analogs to examine inhibition of radiolabeled monoamine uptake. Receptor binding affinities were determined at several TAAR1, serotonergic, adrenergic and dopaminergic receptors and monoamine transporters using difference target-transfected cells.
All fluorinated MDA analogs potently inhibited the NET (IC50 < 1 μM) and had a distinct preference to inhibit 5-HT vs. DA uptake (DAT/SERT= 0.11– 0.65), similar to MDA. However, 3C-BOH and BDB inhibited the NET less potently (IC50= 1.8 – 1.9 μM). BDB was more serotonergic similar to the fluorinated MDA analogs, while 3C-BOH showed a distinct preference to inhibit DA vs. 5-HT uptake (DAT/SERT= 2.3).
N--DEPEA and 4-MePPP potently inhibited the NET (IC50 < 1 μM), with a preference to inhibit DA vs. 5-HT uptake (DAT/SERT=5.5 and DAT/SERT=97, respectively). DPIA inhibited the NET less potently, but selectively inhibit 5-HT vs. DA uptake (DAT/SERT= 0.56), in contrast to the amphetamine-based analogs N--DEPEA and 4-MePPP. Most MDA and amphetamine analogs showed relevant affinity for rat and mouse TAAR1, 1 and 5-HT1A,2A,2C receptors, but not for human TAAR1, monoamine transporters, dopaminergic or 2 receptors.
Fluorinated MDA analogs, BDB, and DPIA, an amphetamine analog, had pharmacological profile similar to MDA, showing potent serotonergic properties. N--DEPEA and 4-MePPP and the MDA analog, 3C-BOH had pharmacological profiles similar to amphetamine showing potent dopaminergic properties. All analogs but N--DEPEA showed possibly relevant 5-HT2A receptor binding.
Karolina E. Kolaczynska is a PhD student working in the field of Psychopharmacology at the University Hospital Basel and University of Basel. Her research focuses on the pharmacological characterization of various novel psychoactive substances (NPS) and investigating the metabolism of hallucinogenic substances using LC-MS/MS methods. Previously, she obtained her undergraduate/masters at the University College London (UCL) in Pharmacology.