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Effect fingerprinting of new psychoactive substances (NPS) using in vitro data

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In this extensive review, Hondebrink et al investigated the available data on in vitro neurotoxicity of the major cathinones, cannabinoids, (hallucinogenic) phenethylamines, arylcyclohexylamines and piperazine derivatives. The obtained effect fingerprints include effects on monoamine reuptake transporters, neurotransmitter receptors and ion channels. In addition to known targets such as inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HT2 receptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines), additional targets could be identified by relating reported effect concentrations to the estimated human brain concentrations during recreational NPS use. This highlights the potential of effect fingerprints for implementation in the risk assessments of NPS (Pharmacology and Therapeutics).