Zanapezil (TAK-147) is a powerful and selective inhibitor of acetylcholine esterase (AChE). It demonstrates significant and reversible inhibition of AChE activity in rat cerebral cortex homogenates (IC50 = 51.2 nM). Furthermore, Zanapezil exhibits moderate inhibition of muscarinic M1 and M2 receptor binding with Ki values of 234 and 340 nM, respectively. This compound holds promise for the investigation of the initial stages of Alzheimer's disease (AD).

Zanapezil (TAK-147) free base is a potent, reversible acetylcholinesterase (AChE) inhibitor with an IC50 of 51.2 nM in rat cerebral cortex homogenates, demonstrating 3.0 and 2.4 times higher efficacy than tacrine and physostigmine, respectively. It minimally inhibits butyrylcholinesterase in rat plasma (IC50 of 23,500 nM), moderately inhibits noradrenaline and serotonin uptake (IC50 values of 4020 nM and 1350 nM, respectively), and affects ligand binding to alpha-1, alpha-2, and serotonin 2 receptors (Ki values of 324, 2330, and 3510 nM, respectively)[1].

Administering Zanapezil (TAK-147), as a free base orally at 3 mg/kg, significantly increased the turnover rates of dopamine, noradrenaline, and serotonin in the rat brain, while doses from 1 to 10 mg/kg led to a statistically significant, dose-dependent reduction in AChE activity in the rat cerebral cortex, as observed in ex vivo experiments[1]. Additionally, Zanapezil at doses of 5 and 10 mg/kg notably raised acetylcholine (ACh) levels in the ventral hippocampus (VH) for 120 minutes in male Wistar rats aged 7 weeks (230-240 g)[2].