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.
Prenatal exposure to ketamine or its analog 2-fluorodeschloroketamine disrupts mitochondrial energy production in developing brain cells, increasing the risk of neurological damage. Using human cerebral organoids and single-cell RNA sequencing of 83,436 cells, the study found that both substances altered gene networks controlling mitochondrial oxidative phosphorylation in cortical cells. Experiments in fetal mouse neurons confirmed that exposure increased mitochondrial fragmentation and oxidative stress while reducing ATP production capacity. These energy disruptions during rapid brain development can make offspring more vulnerable to neurological issues. The results provide direct evidence of neurodevelopmental toxicity from these substances and identify mitochondrial dysfunction as a probable primary molecular mechanism.
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.