Two synthetic dissociative drugs, 4-MeO-PCP and 3-MeO-PCMo, produce rewarding and reinforcing effects in rats, indicating potential for abuse in humans. Both drugs induced conditioned place preference and self-administration, but only 4-MeO-PCP caused locomotor sensitization. Blocking dopamine D1 or D2 receptors prevented the drugs' rewarding effects. The drugs altered dopamine-related proteins and increased delta and gamma brain wave activity, effects also blocked by dopamine antagonists. These findings suggest the drugs' abuse potential is mediated through the mesolimbic dopamine system.
Three novel analogs of methoxetamine (MXE), an NMDA receptor antagonist related to ketamine, showed antidepressant-like effects in mice. The compounds—NENK, 2-MeO-NEK, and 4-MeO-NEK—reduced immobility time in the forced swimming and tail suspension tests, indicating reduced behavioral despair. Their effects were blocked by an AMPA receptor antagonist (NBQX) and a 5-HT2 receptor antagonist (ketanserin), suggesting involvement of both glutamatergic and serotonergic systems. The analogs also altered mRNA levels of AMPA receptor subunits and brain-derived neurotrophic factor in the hippocampus and prefrontal cortex. These findings suggest the compounds may offer rapid antidepressant effects, though further research is needed.