As previously mentioned, the primary challenge associated with the drug discovery of THA-based compounds lies in the hepatotoxicity of the parent molecule. To address this issue, we have recently developed several derivatives , including 7-phenoxytacrine (7-PhO-THA) (Figure ) . This compound combines dual inhibitory effects on AChE and NMDARs with favorable pharmacological properties. It selectively inhibits GluN1/GluN2B receptors via the ifenprodil-binding site and exhibits voltage-dependent inhibition of both GluN1/GluN2A and GluN1/GluN2B subunits. Furthermore, 7-PhO-THA demonstrates neuroprotective efficacy in vivo without causing behavioral side effects typical for NMDAR antagonists. A key advantage of 7-PhO-THA and its derivatives lies in the substitution of position 7 of the basic THA scaffold, which prevents the formation of metabolites such as 7hydroxytacrine (7-OH-THA) and its quinone methide derivative. These undesirable products are major contributors to the hepatotoxicity of THA. However, not all modifications at position 7 led to similar results. For instance, 7-MEOTA, designed to avoid liver biotransformation, still produces 7-OH-THA during metabolism, highlighting the complexity of addressing THA-related toxicity .