Neuropharmacological characterization of the new psychoactive substance methoxetamine
Neuropharmacology September 1, 2017 L. Hondebrink, E. Kasteel, A. Tukker et al.
Methoxetamine (MXE), a ketamine analogue used as a new psychoactive substance, has multiple neuropharmacological effects. In rat primary cortical cells, 10 µM MXE increased glutamate-evoked calcium influx, while ketamine did not. Both MXE and ketamine inhibited spontaneous neuronal activity, with IC50 values of 0.5 µM and 1.2 µM respectively. In human SH-SY5Y cells, MXE slightly reduced calcium increases triggered by potassium and acetylcholine. In human stem cell-derived neurons, MXE only slightly reduced ATP-evoked calcium increases and inhibited spontaneous activity at higher concentrations. MXE also potently blocked human monoamine transporters, especially the serotonin transporter (SERT, IC50 2 µM), followed by norepinephrine (NET, 20 µM) and dopamine (DAT, 33 µM). These in vitro findings provide initial insight into MXE's mechanisms of action.