Tacrine (THA; 1,2,3,4-tetrahydro-9-aminoacridine) was the first FDA-approved drug for the treatment of Alzheimer's disease (AD). Its primary mechanism involves the inhibition of acetylcholinesterase (AChE; E.C. 3.1.1.7), indirectly stimulating the cholinergic system. However, its mode of action is more intricate, encompassing interactions with additional targets, including NMDARs, muscarinic, nicotinic receptors, and others . Although its clinical use was discontinued in 2013 due to hepatotoxicity , the THA scaffold remains a pivotal pharmacophore in medicinal chemistry .