The drug 2-fluorodeschloroketamine (2-FDCK), a ketamine substitute used by drug abusers, shows abuse potential comparable to ketamine. In mice, 2-FDCK at 3 mg/kg induced conditioned place preference, similar to ketamine. Acute injections at 30 mg/kg increased locomotor activity, and repeated treatments led to locomotor sensitization after withdrawal. 2-FDCK supported self-administration at 0.5 mg/kg/infusion, matching ketamine, with peak seeking at 1 mg/kg. In drug discrimination tests, 2-FDCK dose-dependently substituted for ketamine with comparable potency. These findings indicate that 2-FDCK has an abuse potential similar to ketamine.
25C-NBOMe, a high-potency psychedelic acting on the 5-HT2A receptor, reduced cell viability in SH-SY5Y, PC12, and SN4741 cells with IC50 values of 89, 78, and 62 μM, respectively. Methamphetamine reduced viability at millimolar IC50 values in the same tests, making 25C-NBOMe over 50 times more potent than methamphetamine in reducing SH-SY5Y cell viability. 25C-NBOMe increased phosphorylated ERK expression and decreased phosphorylated Akt and phosphorylated Ser9-GSK3β. GSK3β inhibitors or MEK inhibitors prevented 25C-NBOMe-induced neurotoxicity, suggesting inhibition of the Akt pathway and activation of the ERK cascade are involved.