omega-agatoxin IVA and excitotoxicity in cortical neuronal cultures

Because the P- and Q-type Ca2+ channel antagonist omega-agatoxin IVA inhibits glutamate release, agatoxin-related drugs could have a role in the treatment of excitotoxic neurologic disorders such as stroke. We examined the effect of omega-agatoxin IVA on excitotoxicity (lactate dehydrogenase release) induced by depolarization with veratridine or ouabain, or by N-methyl-D-aspartate, in neuron-enriched cerebral cortical cultures. omega-Agatoxin IVA (< or = 300 nM) failed to reduce excitotoxicity, as did the L-type Ca2+ channel antagonist nimodipine and the N-type antagonist omega-conotoxin GVIA. Drugs that inhibit glutamate release may not necessarily be neuroprotective.