Abstract
The synthesis and pharmacology of 6-amino-1,4-dihydropyridines, such as ethyl 6-amino-4-aryl-5-cyano-1,4-dihydro-2-methyl-3-pyridinecarboxylic acids (3-16) and 2-amino-4-aryl-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydro-3-quinolinenitriles (17-21) are described. Compounds 18 and 21, at the concentration of 0.3 microM, proved to be the best blockers of the [Ca(2+)] overload induced by depolarization with high [K(+)] of SH-SY5Y neuroblastoma cells, with values of 63.8% and 50.4%, respectively. Most of the compounds induced a remarkable neuroprotective effect against toxicity caused by high [K(+)]-elicited [Ca(2+)] overload, and against H(2)O(2)-generated free radicals, in SH-SY5Y cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcium / metabolism*
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Calcium Channels / metabolism
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Cell Death / drug effects
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Cell Line, Tumor
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Dihydropyridines / chemical synthesis*
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Dihydropyridines / chemistry
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Dihydropyridines / pharmacology*
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Humans
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Hydrogen Peroxide / metabolism
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Lactic Acid / metabolism
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Neurons / cytology*
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Neurons / drug effects*
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Neurons / metabolism
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Neuroprotective Agents / chemical synthesis*
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Oxidoreductases / metabolism
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Potassium / metabolism
Substances
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Calcium Channels
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Dihydropyridines
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Neuroprotective Agents
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Lactic Acid
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1,4-dihydropyridine
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Hydrogen Peroxide
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Oxidoreductases
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Potassium
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Calcium