The escalating prevalence
of new psychoactive substances
(NPSs)
poses a significant public health challenge, evidenced by the vast
chemical diversity, with over 500 substances reported annually to
the United Nations Office on Drugs and Crime-Early Warning Advisory
(UNODC-EWA) in the past five years. Among NPSs, synthetic cathinones
are gaining a lot of popularity among users. Notably, synthetic cathinones
accounted for approximately 50% of the total quantity of NPSs reported
as seized by EU Member States in 2021. Preliminary data from UNODC
indicates that a total of 209 synthetic cathinones have been reported
to date. As their popularity grows, studying the structure–activity
relationship (SAR) of synthetic cathinones is essential. SAR studies
elucidate how structural features impact biological effects, aiding
in toxicity prediction, regulatory compliance, and forensic identification.
Additionally, SAR studies play a pivotal role in guiding drug policies,
aiding authorities in categorizing and regulating newly emerging synthetic
cathinones, mitigate public health risks and offer valuable insights
into potential therapeutic applications. Thus, our Review consolidates
recent findings on the effects of different substitutions in the chemical
scaffold of synthetic cathinones on their mechanism of action as well
as pharmacological and toxicological effects of synthetic cathinones,
thus enhancing understanding of the SAR of synthetic cathinones’
pharmacology and potential implications.