dizocilpine-maleate and serofendic-acid

Analogues of serofendic acid were prepared and their protective effects against L-glutamate (Glu)-induced neurotoxicity were examined using primary cultures of rat cortical neurons. Some analogues exhibited similar neuroprotective activity to that of serofendic acid.

Topics: Animals; Cells, Cultured; Diterpenes; Glutamic Acid; Neurons; Neuroprotective Agents; Neurotoxicity Syndromes; Rats; Structure-Activity Relationship

We have previously reported that a novel neuroprotective substance named serofendic acid was purified and isolated from ether extract of fetal calf serum. In the present study, we investigated the effect of serofendic acid on acute neurotoxicity induced by L-glutamate (Glu) using primary cultures of rat cortical neurons. Exposure of cortical cultures to Glu for 1 h caused a marked decrease in cell viability, as determined by trypan blue exclusion. This acute Glu neurotoxicity was prevented by N-methyl-D-aspartate (NMDA) receptor antagonists, extracellular Ca(2+) removal, nitric oxide (NO) synthase inhibitor and NO scavenger. Serofendic acid prevented acute Glu neurotoxicity in a concentration-dependent manner. Acute neurotoxicity was induced by ionomycin, a Ca(2+) ionophore, and S-nitroso-L-cysteine, an NO donor. Serofendic acid also prevented both ionomycin- and S-nitroso-L-cysteine-induced neurotoxicity. Moreover, the protective effect of serofendic acid on acute Glu neurotoxicity was not affected by cycloheximide, a protein synthesis inhibitor, and actinomycin D, an RNA synthesis inhibitor. These results indicate that serofendic acid protects cultured cortical neurons from acute Glu neurotoxicity by reducing the cytotoxic action of NO and de novo protein synthesis is not required for this neuroprotection.

Topics: Animals; Calcium; Cattle; Cell Survival; Cells, Cultured; Cerebral Cortex; Cysteine; Diterpenes; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Combinations; Fetal Blood; Fetus; Ionomycin; Neurons; Neurotoxicity Syndromes; Nitric Oxide; Quinoxalines; Rats; S-Nitrosothiols; Sodium Glutamate; Time Factors; Valine