Reexamining the Use of Tacrine for Neurological Diseases

Tacrine was originally brought to the market in 1993 as an acetylcholinesterase inhibitor to fight the symptoms of Alzheimer disease.

Introduction

Patients who develop neurologic disorders require a complicated array of medications. The common culprit leading to these diseases is the worsening condition of certain neurotransmitter systems and malfunctioning neural networks.

Researchers from universities around the Middle East have completed a review article to examine small molecules to treat Alzheimer disease (AD). They specifically looked at the acetylcholinesterase inhibitor tacrine.

Tacrine was originally brought to the market in 1993 as an acetylcholinesterase inhibitor to fight the symptoms of AD, although manufacturers would withdraw it in 2013 due to hepatic toxicities. Acetylcholinesterase inhibitors have cholinergic actions but can modulate muscarinic and nicotinic receptors.

Ongoing research indicates that tacrine targets a wider array of pathways than previously believed, opening the doors for investigators to explore potential benefits of the drug for other conditions.

Key Findings

Research reveals some novel uses for tacrine—for example, it seems to mitigate ketamine’s adverse effects. It may also address delirium and psychological disturbances during the period immediately after administering anesthesia.

An interesting finding is the use of a hybrid of tacrine and melatonin, using the rationale that melatonin’s ability to neutralize free radicals would be advantageous. In people with neurological disorders, tacrine significantly increases cerebral blood flow, a significant discovery for stopping future neurologic diseases.

An additional area of great interest is pairing nitric oxide with tacrine analogs to increase blood flow and decrease inflammatory responses. The increase of blood flow to the brain is essential for neurologic diseases.

Tacrine Derivatives

Investigators all over the world are looking for tacrine derivatives as possible future treatment options. Different researchers have looked at its structure and made substitutions on its ring, bound it to other compounds to reduce toxicity, and made similar molecular alterations to improve safety, tolerability, and efficacy.

Some of these compounds modulate neurogenesis; some modulate neuroinflammation; and some modulate endoplasmic stress, apoptosis (programmed cell death), energy metabolism, and calcium homeostasis. These findings could be groundbreaking in the quest to treat many different diseases.

Therapeutic Benefit

These findings could mean major progress in the fight to mitigate or cure AD and possibly many other diseases with no cure. The discovery of linking tacrine to a ligand may improve its risk benefit profile and may lead to tremendous therapeutic potential.

Conclusion

The newer versions of tacrine are in preclinical trials, not human trials, but it is moving in the right direction. On top of reconsidering tacrine for the treatment of AD, researchers have used tacrine as a tool to induce Parkinson disease in animals to then test other drugs for efficacy. All of this means that tacrine-like drugs may hopefully someday make their way to the market and change many lives.

About the Author

Christina Nault is a 2025 PharmD candidate at the University of Connecticut.

Reference

Mitra S, Muni M, Shawon NJ, et al. Tacrine Derivatives in Neurological Disorders: Focus on Molecular Mechanisms and Neurotherapeutic Potential. Oxid Med Cell Longev. 2022;2022:7252882. Published 2022 Aug 18. doi:10.1155/2022/7252882