"In general, synthetic cathinones are classified as stimulants or amphetamine-type stimulants [109, 110]. However, the pharmacological effects of individual derivatives are strictly dependent on the type of substituents and their location, and the differences in pharmacological profiles between individual cathinone derivatives are considerable. The range of pharmacological profiles of cathinone derivatives varies from those resembling MDMA and cocaine in action, through cathinone derivatives possessing methamphetamine-like psychostimulant effects, to highly dopaminergic pyrovalerone cathinone derivatives [110, 111]. The structure differs depending on the lipophilicity and steric expansion, which affects the pharmacokinetic aspects, but also the key interaction with monoamine transporters (MATs) in the central nervous system [112, 113]. The main systems involved are dopaminergic, serotonergic and noradrenergic, and the main mechanism of their modulation is the interaction with particular transporters, including dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). Synthetic cathinones alter neurotransmitter concentrations by acting as MAT inhibitors or substrates, inducing efflux of endogenous neurotransmitters [110, 111, 114]. Dopaminergic activity is mainly associated with stronger reinforcing effects and abuse liability. In contrast, serotonergic activity is identified with entactogenic effects similar to those of MDMA [111,112,113, 115, 116]. Pyrrolidine cathinone derivatives are particularly potent dopaminergic, while methylone, similar in structure to MDMA, exhibits serotonergic effects; cathinone derivatives substituted at the phenyl ring in the para position also exhibit comparable activity [117]. The strength of action on the noradrenergic system is more or less equal among particular synthetic cathinones; therefore, the main factor distinguishing the action of particular derivatives is selectivity toward DAT and SERT [111]. Depending on the structure of the derivative, the interaction with individual monoaminergic systems is characterized by different strength and selectivity, which translates into desired effects and intoxication symptoms. The main effects of cathinone use include symptoms from the cardiovascular system such as tachycardia and increased blood pressure, and from the nervous system such as euphoria and motor excitation, as well as hyperthermia [7, 118,119,120,121]. In addition to psychostimulant effects, some synthetic cathinones may have hallucinogenic properties similar to MDMA. Synthetic cathinones possessing high selectivity toward the serotonin system may lead to a dangerous serotonergic syndrome resulting from excessive activation of 5-HT2A receptors. Most often, however, the appearance of this type of intoxication results from combined drug intoxication, mainly in combination with selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs) [7, 122, 123]."


Kuropka, P., Zawadzki, M. & Szpot, P. A review of synthetic cathinones emerging in recent years (2019–2022). Forensic Toxicol 41, 25–46 (2023). doi.org/10.1007/s11419-022-00639-5.