Stimulant mechanisms of cathinones — Effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices

Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances – The case of the benzofuran 5-MAPB

“…It achieves that through the real time (sub-second) analysis of dopamine efflux following electrical stimulation before-and-after a drug application, as we have demonstrated for a range of cathinones (Opacka-Juffry et al, 2014). The present study revealed that 5-MAPB can cause reverse transport and also increases the AUC of electrically evoked dopamine efflux.…”

Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats

“…Interestingly, 5-HT 2C receptor antagonism is thought to be a reason that fluoxetine (Prozac) does not produce the degree of anxiety during initial dosing that often plagues other selective serotonin reuptake inhibitors (SSRIs) [Pälvimäki et al, 1996]. Thus, S -MEPH may work through a dual 5-HT-based mechanism to mitigate psychostimulant withdrawal, with a 5-HT 2C receptor block underlying its anxiolytic efficacy and an increase in 5-HT release through its monoamine substrate actions underlying its antidepressant effect [Baumann et al, 2012; Eshleman et al, 2013; Gregg et al, 2015; López-Arnau et al, 2012; Opacka-Juffry et al, 2014]. A role for 5-HT 2 receptors in the antidepressant effects of S -MEPH is also possible because 5-HT 2A and 5-HT 2C receptors facilitate depressive-like behavior in preclinical studies [Diaz and Maroteaux, 2011; Patel et al, 2004].…”

“…Mechanistically, synthetic cathinones have been classified according to two distinct actions on the monoamine system. One class is comprised of substrate-type releasers, such as mephedrone (4-methylmethcathinone, MEPH), that enter the presynaptic neuron and promote transporter-mediated release of dopamine (DA) and serotonin (5-HT) [Baumann et al, 2012; Eshleman et al, 2013; López-Arnau et al, 2012; Opacka-Juffry et al, 2014]. In vivo microdialysis studies have shown that the substrate action of MEPH increases extracellular DA and 5-HT in the nucleus accumbens of rats [Baumann et al, 2012; Kehr et al, 2011].…”

How preclinical studies have influenced novel psychoactive substance legislation in the UK and Europe

“…As detailed above, when NPS started flooding the market over the last decade or so, preclinical tests were exploited to compare these substances to their traditional counterpart, describing them as cocaine ‐like or amphetamine‐like substances . Unlike known illicit substances such as methamphetamine and MDMA (3,4‐methylenedioxymethamphetamine), the pharmacology related to emerging NPS is scarce and may not suitably be extrapolated from existing knowledge.…”

“…As detailed above, when NPS started flooding the market over the last decade or so, preclinical tests were exploited to compare these substances to their traditional counterpart, describing them as cocaine-like or amphetamine-like substances. 60,130 Unlike known illicit substances such as methamphetamine and The validity of animal models in understanding the harmful effects of illicit substances in humans is well established and therefore, can provide a predictive validity for NPS-related harms. For instance, ketamine has been associated with bladder toxicity.…”