G. C. Palmer, J. Hutchison
1997
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Abstract
Publisher Summary Remacemide hydrochloride was discovered from a chemical series employing a rational synthetic approach based on molecular modeling. Remacemide hydrochloride was effective orally, regarding prevention of seizures evoked by maximal electroshock (MES) in rodents. Remacemide hydrochloride and ARL12495AA inhibit seizures induced by N-methyl- D -aspartate (NMDA), whereas remacemide hydrochloride alone is active against kainic acid-induced seizures. Neuronal protective properties of remacemide hydrochloride and ARL12495AA were examined in primary cultures from rat cerebral cortex. Treatment of cells with ARL12495AA also reduced the NMDA-elicited loss in membrane-associated protein kinase C activity and the magnitude in the NMDA-triggered Ca2+ surge into the cells. Potential neuroprotective properties for remacemide hydrochloride were demonstrated when pretreatment of mice exposed to anoxic conditions led to an extension of the time to death. Remacemide hydrochloride appeared free of genotoxicity when evaluated in two in vitro tests for mutagenicity.