Remco H S Westerink

Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The Netherlands. Electronic address: r.westerink@uu.nl.

2 papers in the library · 137 citations · publishing 2017-2018

Papers

Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?

Pharmacology & therapeutics February 1, 2018 Laura Hondebrink, Anne Zwartsen, Remco H S Westerink 78 citations

More than 600 new psychoactive substances (NPS) have been reported, yet information on their neuropharmacological and toxicological effects remains limited, hampering risk assessment. A review of in vitro neuronal modes of action created effect fingerprints for frequently reported NPS classes: cathinones, cannabinoids, hallucinogenic phenethylamines, arylcyclohexylamines, and piperazine derivatives. The fingerprints highlight main modes of action—such as inhibition or reversal of monoamine reuptake transporters for cathinones and activation of 5-HT2 receptors for hallucinogenic phenethylamines—and identify additional targets, including dopamine, adrenergic, GABAA, and acetylcholine receptors, by relating effect concentrations to estimated...

DOI: 10.1016/j.pharmthera.2017.10.022 Full text Designer drugs Mechanism of action Receptors Transporters +5

Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay.

Toxicology in vitro : an international journal published in association with BIBRA December 1, 2017 Anne Zwartsen, Anouk H A Verboven, Regina G D M Van Kleef et al. 59 citations

A new high-throughput fluorescent assay can detect how illicit drugs and new psychoactive substances (NPS) inhibit monoamine reuptake transporters (DAT, NET, SERT). The assay uses a fluorescent monoamine-mimicking substrate in human embryonic kidney cells expressing these transporters. It successfully discriminated between common drugs (cocaine, amphetamine, MDMA), several NPS (e.g., α-PVP, 2C-B, 25B-NBOMe), and the antidepressant fluoxetine. Most IC50 values matched those from traditional radiometric assays and estimated human brain concentrations, though phenethylamines showed higher IC50 values on SERT, possibly due to experimental differences. The fluorescent assay is simpler, works under physiological conditions, requires no special facilities, and allows kinetic measurements, making it a good alternative to radiometric methods.

DOI: 10.1016/j.tiv.2017.05.010 Full text Designer drugs Dopamine transporter Drug screening Fluorescent monoamine substrate +2