Effects of intranasal administration of meserine on AChE activity and scopolamine-induced amnesia in mice

Abstract

Abstract: AIM: The present study was designed to assess the effects of a novel cholinesterase inhibitor Meserine on cholinesterase activity and cognitive impairment induced by scopolamine in mice.METHODS: Mouse brain homogenate, mouse plasma and recombinant human AChE (rHuAChE) were used to assess the cholinesterase inhibitory activity, selectivity and enzyme kinetics of Meserine in vitro. The AChE activity and ACh level in mice brain were measured to evaluate the in vivo effect of Meserine on brain cholinergic system. Passive avoidance testand Morris water maze test were utilized to verify the efficacy of Meserine on scopolamine-induced amnesia in mice.RESULTS: Meserine possessed good inhibitory activity against AChE and BuChE, with IC₅₀ of (65.2±3.2) nmol/L and (86.7±4.9) nmol/L, respectively. Enzyme kinetics study showed that Meserine was a noncompetitive inhibitor on rHuAChE. After intranasal administration of Meserine, the AChE inhibition and ACh level in brain changed consistently. The peak of AChE inhibition (26.9%) and ACh level (1269.0 ng/g) were reached around 15 min after administration. The results of behavior tests showed that Meserine (10 μg/kg, i.n.) could significantly reverse the cognitive impairments induced by scopolamine in mice (P<0.01 vs Scop) .CONCLUSION: Our results suggested that Meserine was a potent noncompetitive cholinesterase inhibitor. Intranasal administration of Meserine could effectively ameliorate the scopolamine-induced amnesia in mice via modulating brain cholinergic system.

Key words: Alzheimer's disease, Meserine, Cholinesterase inhibitor, Scopolamine, Multi-target- directed ligand

CLC Number:

R965.2

JIANG Pan, ZHENG Zhao-xi, SHAO Bi-yun, ZHANG Qi-zhi, XIE Qiong, QIU Zhui-bai, WANG Hao. Effects of intranasal administration of meserine on AChE activity and scopolamine-induced amnesia in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(9): 969-975.

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