Abstract
Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.
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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4-Aminopyridine / analogs & derivatives*
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4-Aminopyridine / chemistry
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Alzheimer Disease / drug therapy
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Aminopyridines / chemical synthesis
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Aminopyridines / therapeutic use
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Aminopyridines / toxicity
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Amnesia / chemically induced
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Amnesia / drug therapy*
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Animals
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Avoidance Learning
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Carbon Dioxide
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Indoles / chemical synthesis
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Indoles / therapeutic use
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Indoles / toxicity
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Male
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Mice
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Nootropic Agents / chemical synthesis*
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Nootropic Agents / therapeutic use
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Piracetam / therapeutic use
Substances
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(3-(pyridin-4-ylcarbamoyl)propyl)carbamic acid tert-butyl ester
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3-(4-aminopyridin-3-ylmethylene)-1,3-dihydroindol-2-one
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4-amino-N-pyridin-4-ylbutyramide
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Aminopyridines
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Indoles
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Nootropic Agents
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Carbon Dioxide
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4-Aminopyridine
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Piracetam