Repeated ketamine exposure in neonatal rats reduces levels of DISC1 and several signaling proteins (pGSK-3β, β-catenin, pERK, pCREB, PSD95), leading to neuroapoptosis, inhibited neurite growth, and cognitive deficits in adolescence. Lithium treatment upregulates DISC1 and activates the GSK-3β/β-catenin and ERK/CREB pathways, thereby ameliorating these harmful effects. The findings suggest lithium may protect against ketamine-induced long-term neurotoxicity during brain development.
Using mass spectrometry and theoretical calculations, 17 oxidative metabolites of the drug 2-fluorodeschloroketamine (2-FDCK) were identified in human urine and grouped into four categories. The study clarified how the site of oxidative metabolism relates to the electron cloud density in the molecule. Two mirror-image forms of a related compound, dihydro-2-FDCK, were distinguished using a lab-made reference standard and computational predictions. The work also revealed which enzymes favor particular molecular shapes during hydrogenation in the body. These findings provide a foundation for identifying metabolites of similar ketamine-type drugs.