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 Ki 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].

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> AChE

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]. Animal Model: Male Wistar rats 7 weeks in age (230-240 g)[2] Dosage: 5 and 10 mg/kg Administration: Oral administration Result: Increased acetylcholine (ACh) level in the VH for 120 min.

[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.