The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative

Pyrovalerone cathinones are potent psychoactive substances that possess a pyrrolidine moiety. Pyrovalerone-type novel (NPS) continuously detected but their pharmacology and toxicology largely unknown. We assessed several pyrovalerone related cathinone derivatives at the human norepinephrine (NET), dopamine (DAT), serotonin (SERT) uptake transporters using HEK293 cells overexpressing each respective transporter. examined transporter-mediated monoamine efflux in preloaded cells. The receptor binding activation potency was also 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C receptors. All were DAT (IC50 = 0.02–8.7 ?M) NET inhibitors 0.03–4.6 ?M), exhibited no SERT activity concentrations < 10 ?M. None of compounds induced efflux. NEH DAT/NET inhibitor 0.17–0.18 ?M). 4F-PBP high selectivity for (DAT/SERT ratio 264–356). Extension alkyl chain enhanced inhibition potency, while presence 3,4-methylenedioxy moiety increased potency. Most did not exhibit any relevant other In conclusion, selective indicating these likely produce strong psychostimulant effects have abuse liability.