Tacrine hydrochloride hydrate

Tacrine hydrochloride hydrate (CAS No. 206658-92-6) is the hydrochloride hydrate form of Tacrine (CAS No. 321-64-2, Catalog No.: BA8455). As the first-generation oral cholinesterase inhibitor, its core targets are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). It competitively binds to the catalytic active site and peripheral anionic site of the enzymes, inhibiting acetylcholine hydrolysis to increase its concentration in the synaptic cleft. Meanwhile, it can inhibit Aβ aggregation and excessive tau phosphorylation, exerting neuroprotective effects. Its IC₅₀ value against human AChE is 320 nM. The commonly used application concentration ranges from 0.1 to 10 μM (for in vitro enzyme inhibition assays, cytotoxicity studies, and neuroprotective research). The clinically effective therapeutic concentration corresponds to an oral dosage of 40 mg/day (administered in multiple divided doses). It was previously used for the treatment of mild to moderate Alzheimer's disease (AD) and could improve patients' cognitive function, but was withdrawn from the market in 2013 due to severe hepatotoxicity (elevated liver transaminases). Its low molecular weight and simple structure make it an important scaffold for the development of multi-target AD drugs, and its derivatives (such as 6-chlorotacrine) can reduce toxicity and enhance activity.

References:

[1] Bubley A, Erofeev A, Gorelkin P, Beloglazkina E, Majouga A, Krasnovskaya O. Tacrine-Based Hybrids: Past, Present, and Future. Int J Mol Sci. 2023 Jan 15;24(2):1717. doi: 10.3390/ijms24021717. PMID: 36675233; PMCID: PMC9863713.