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...
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.
Neurotoxicology
May 1, 2018
Anne Zwartsen, Laura Hondebrink, Remco Hs Westerink
42 citations
All eight new psychoactive substances (PMMA, α-PVP, methylone, MDPV, 2C-B, 25B-NBOMe, BZP, TFMPP) and two classic illicit drugs (cocaine, methamphetamine) rapidly and concentration-dependently decreased the weighted mean firing rate and weighted mean burst rate of rat primary cortical cultures grown on multi-well microelectrode arrays during a 30-minute acute exposure. Cocaine most potently inhibited firing (IC50 9.8 μM), while methamphetamine and PMMA were much less potent (IC50 100 μM and 112 μM). Among cathinones, MDPV and α-PVP had comparable IC50 values (29 μM and 21 μM), but methylone was 10-fold less potent (IC50 235 μM).
Neurotoxicology
September 1, 2019
Anne Zwartsen, Laura Hondebrink, Remco Hs Westerink
22 citations
The effects of several new psychoactive substances (NPS) and illicit drugs on neuronal activity were tested in rat brain cells grown on microelectrode arrays. After 30 minutes of exposure, all compounds reduced neuronal activity in a dose-dependent manner. Extending exposure to 5 hours did not cause further decreases. After a 19-hour washout period, activity fully recovered only for methamphetamine, cocaine, and benzylpiperazine; partially recovered for MDMA, PMMA, and α-PVP; and did not recover at the highest concentrations of MDPV, 2C-B, 25B-NBOMe, and TFMPP. Low concentrations of methylone and 2C-B actually increased activity after washout. The ability of neural networks to regain activity after drug exposure appears unrelated to drug class or potency. Complete recovery was rare, which is concerning.