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 Ki values of 324, 2330 and 3510 nM, respectively[1].
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].
[1]. K Hirai, et al. Neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, in rats. J Pharmacol Exp Ther. 1997 Mar;280(3):1261-9.
[2]. Izzettin Hatip-Al-Khatib,et al. Comparison of the effect of TAK-147 (zanapezil) and E-2020 (donepezil) on extracellular acetylcholine level and blood flow in the ventral hippocampus of freely moving rats. Brain Res. 2004 Jun 25;1012(1-2):169-76.