SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

• Published in: Biological & pharmaceutical bulletin Vol. 41; no. 3; pp. 427 - 434
• Main Authors: Sheng, Gaofeng, Zhang, Jinlin, Gao, Shengfeng, Gu, Yuanyuan, Jiang, Bo, Gao, Qiufang
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2018; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Alzheimer's disease; Brain-derived neurotrophic factor; Chemical compounds; Cognitive ability; Dementia; Dementia disorders; Enzyme inhibitors; Hippocampus; memory; Mental task performance; Protein-tyrosine kinase; Scopolamine; SKF83959; TrkB receptors; Water treatment; Western blotting; SKF83959; memory; brain-derived neurotrophic factor; scopolamine
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b17-00877

Patients with Alzheimer’s disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.