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Synthesis, biological evaluation, and computational studies of tri- and tetracyclic nitrogen-bridgehead compounds as potent dual-acting AChE inhibitors and hH3 receptor antagonists

Darras, Fouad ; Pockes, Steffen ; Huang, Guozheng ; Wehle, Sarah ; Strasser, Andrea ; Wittmann, Hans-Joachim ; Nimczick, Martin ; Sotriffer, Christoph ; Decker, Michael



Abstract

Combination of AChE inhibiting and histamine H3 receptor antagonizing properties in a single molecule might show synergistic effects to improve cognitive deficits in Alzheimer's disease, since both pharmacological actions are able to enhance cholinergic neurotransmission in the cortex. However, whereas AChE inhibitors prevent hydrolysis of acetylcholine also peripherally, histamine H3 antagonists ...

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