• Bi-Yun Shao, Zheng Xia, Qiong Xie, Xin-Xing Ge, Wei-Wei Zhang, Jian Sun, Pan Jiang, Hao Wang, Wei-Dong Le, Zhui-Bai Qiu, Yang Lu, and Hong-Zhuan Chen.
• Department of Pharmacology & Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
• CNS Neurosci Ther. 2014 Feb 1; 20 (2): 165-71.

AimsTo investigate whether Meserine, a novel phenylcarbamate derivative of (-)-meptazinol, possesses beneficial activities against cholinergic deficiency and amyloidogenesis, the two major pathological characteristics of Alzheimer's disease (AD).MethodsEllman's assay and Morris water maze were used to detect acetylcholinesterase (AChE) activity and evaluate spatial learning and memory ability, respectively. Both high content screening and Western blotting were carried out to detect β-amyloid precursor protein (APP), while RT-PCR and ELISA were conducted to detect APP-mRNA and β-amyloid peptide (Aβ).ResultsIn scopolamine-induced dementia mice, Meserine (1 mg/kg, i.p.) significantly ameliorated spatial learning and memory deficits, which was consistent with its in vitro inhibitory ability against AChE (recombinant human AChE, IC50 = 274 ± 49 nM). Furthermore, Meserine (7.5 mg/kg) injected intraperitoneally once daily for 3 weeks lowered APP level by 28% and Aβ42 level by 42% in APP/PS1 transgenic mouse cerebrum. This APP modulation action might be posttranscriptional, as Meserine reduced APP by about 30% in SH-SY5Y-APP695 cells but did not alter APP-mRNA level. And both APP and Aβ42 lowering action of Meserine maintained longer than that of rivastigmine.ConclusionMeserine executes dual actions against cholinergic deficiency and amyloidogenesis and provides a promising lead compound for symptomatic and modifying therapy of AD.© 2013 John Wiley & Sons Ltd.

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