Abstract
In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on beta-carbolines (BCs). 6-Oxygenated beta-carboline and beta-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / metabolism*
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Alzheimer Disease / drug therapy*
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Butyrylcholinesterase / metabolism*
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Carbolines / chemistry
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Carbolines / pharmacology*
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Carbolines / therapeutic use
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Cholinesterase Inhibitors / therapeutic use*
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Galantamine / pharmacology
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Humans
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Inhibitory Concentration 50
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Phenylcarbamates / pharmacology
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Physostigmine / pharmacology
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Rivastigmine
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Serotonin / metabolism
Substances
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Carbolines
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Cholinesterase Inhibitors
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Phenylcarbamates
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Galantamine
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Serotonin
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Physostigmine
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Acetylcholinesterase
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Butyrylcholinesterase
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Rivastigmine