Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non-hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.

Automated summary

The review highlights recent developments in identifying new tacrine analogues for Alzheimer's disease therapy, focusing on non-hepatotoxic tacrines and the design of multitarget tacrines. Tacrine, the first approved cholinesterase inhibitor for AD, did not stop disease progression and had significant hepatotoxic effects, leading to its withdrawal from clinical use. Efforts are now being made to develop safer tacrine derivatives and multitarget compounds to target other biological mechanisms involved in AD.