Zanapezil (free base)

Zanapezil (TAK-147) free base is a potent, reversible and selective acetylcholine esterase (AChE) inhibitor. Zanapezil free base shows a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC₅₀=51.2 nM). Zanapezil free base shows a moderate inhibition of muscarinic M1 and M2 receptor binding with K_i values of 234 and 340 nM, respectively. Zanapezil free base can be used for the research of early stages of Alzheimer's disease (AD)^[1]. In Vitro: Zanapezil (TAK-147) free base shows a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC₅₀=51.2 nM), and is 3.0- and 2.4-fold more potent than tacrine and physostigmine, respectively. Zanapezil free base is the least potent inhibitor of butyrylcholinesterase activity in rat plasma (IC₅₀=23,500 nM)^[1].
Zanapezil free base moderately inhibits uptake of noradrenaline and serotonin with IC₅₀ values of 4020 and 1350 nM, respectively^[1].
Zanapezil free base also inhibits ligand binding at alpha-1, alpha-2 and serotonin 2 receptors with K_i values of 324, 2330 and 3510 nM, respectively^[1]. In Vivo: Oral administration of Zanapezil (TAK-147; 3 mg/kg) free base significantly accelerated the turnover rates of dopamine, noradrenaline and serotonin in the rat brain. Oral administration of Zanapezil free base at doses ranging from 1 to 10 mg/kg induces a statistically significant and dose-dependent decrease in AChE activity in the cerebral cortex in ex vivo experiments^[1].
Zanapezil (TAK-147; 5 and 10 mg/kg) free base significantly increases ACh level in the ventral hippocampus (VH) for 120 min^[2].