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Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/3720
Title: Neurochemical and neuropharmacological characterization of novel dimeric acetylcholinesterase inhibitors for Alzheimer's disease
Authors: Ho, Wing Lok
Issue Date: 1999
Abstract: The general procedure of neurochemical characterization of memory enhancing properties of novel dimeric acetylcholinesterase inhibitors (AChEI) was presented in this thesis. Considering the cholinergic hypothesis as the only current promising approach to the palliative treatment of Alzheimer's disease (AD), screening for novel AChEI with higher potency and selectivity from combinatory chemistry to traditional Chinese herbs is highly demanded. To clarify the improved potency and selectivity of dimeric AChEI (his(7)-tacrine) proposed by Pang, efforts were made to synthesize new compounds based on the dual binding site hypothesis of the enzyme acetylcholinesterase (AChE). Two units of tacrine were linked together via a so-called "tether" in appropriate length, which results in significant increase in AChE inhibition potency. Enzymatic assay and kinetic study were employed to demonstrate the biochemical properties of this inhibitor. Memory enhancing effects of the agent were confirmed in rats by animal models including Morris water maze and radial maze under different means of lesion. Bis(7)-tacrine showed promising improvement in the standard memory tasks in both models. The neuropharmacological effects produced by this novel dimeric AChEI are strikingly promising. Further research will be continued with regard to these heterodimers, hoping that the dimeric derivatives of tacrine provide a therapeutic breakthrough to the palliative treatment of AD.
Description: Thesis (M.Phil.)--Hong Kong University of Science and Technology, 1999
xi, 119 leaves : ill. (some col.) ; 30 cm
HKUST Call Number: Thesis BICH 1999 Ho
URI: http://hdl.handle.net/1783.1/3720
Appears in Collections:BICH Master Theses

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