Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second-largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter in monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health.

This study aims to examine the cytotoxicity mechanisms of synthetic cathinone (bath salts) on rat primary cultured neurons and primary astroglial cells, and to assess their neurobehavioral effects on mice. We administered methylenedioxypyrovalerone (MDPV) to both rat primary cultured neurons and primary astroglial cells to assess cell injury. We also analyzed the effects of MDPV on these cell cultures using immunocytochemistry. We utilized western blotting to assess the breakdown of αII-spectrin and glial fibrillary acidic protein (GFAP) induced by MDPV. The western blotting experiment also included calpain and caspase inhibitors (SNJ1945 and Z-D-DCB, respectively) and pro-apoptotic and pro-necrotic agents (Staurosporine and calcium ionophore A23187, respectively). Lastly, we assessed MDPV’s effects on behavioral effects using rotarod, locomotor activity, elevated plus maze, Morris water maze, forced swimming, and open field tests. MDPV caused a dose-dependent release of LDH in both cerebrocortical neuron-astroglia mixed cultures and primary astroglial cultures. MDPV also caused neurite breakages and astroglial process retraction on immunocytochemistry. Lastly, MDPV induced αII-spectrin breakdown in western blotting experiments. Co-administration of calpain and caspase inhibitors reduced the degradation of αII-spectrin and GFAP. MDPV administration also increased anxiety-like behavior and locomotor activity in the mice. Synthetic cathinones, which share structural similarities with methamphetamine, also induce significant neurotoxic effects and neurobehavioral effects on rodent models. These neurotoxic effects are likely mediated by calpain and caspase-induced apoptosis and necrosis, while astroglial death is likely only due to calpain activation. Therefore, further research may focus on pharmacological interventions targeting these pathways to mitigate the cytotoxic impact of cathinones in humans.

The innovation of the new psychoactive substances (NPS) market requires the rapid identification of new substances that can be a risk to public health, in order to reduce the damage due to their use. Twelve seized products suspected to contain illicit substances were analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), gas chromatography coupled to mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). Synthetic cathinones (SCat) were found in all products, either as a single component or in mixtures. Infrared spectra of all products were consistent with the molecular structure of SCat, showing an intense absorption band at 1700–1674 cm‐1, corresponding to the carbonyl stretching, a medium/strong peak at 1605-1580 cm-1, indicating stretching vibrations in the aromatic ring (C=C) and bands with relative low intensity at frequencies near 2700–2400 cm-1, corresponding to an amine salt. It was possible to identify a total of eight cathinone derivatives by GC-MS and NMR analysis: 4’-methyl-α-pyrrolidinohexanophenone (MPHP), α-pyrrolidinohexanophenone (α-PHP), 3-fluoromethcathinone (3-FMC), methedrone, methylone, buphedrone, N-ethylcathinone, and pentedrone. Among the adulterants found in these samples, caffeine was the most frequently detected substance, followed by ethylphenidate. These results highlight the prevalence of SCat in seized materials of the Portuguese market. Reference standards are usually required for confirmation, but when reference materials are not available, the combination of complementary techniques is fundamental for a rapid and an unequivocal identification of such substances.