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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Aug 15;90(16):7894–7897. doi: 10.1073/pnas.90.16.7894

A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia.

K Valentino 1, R Newcomb 1, T Gadbois 1, T Singh 1, S Bowersox 1, S Bitner 1, A Justice 1, D Yamashiro 1, B B Hoffman 1, R Ciaranello 1, et al.
PMCID: PMC47249  PMID: 8102803

Abstract

Calcium influx is believed to play a critical role in the cascade of biochemical events leading to neuronal cell death in a variety of pathological settings, including cerebral ischemia. The synthetic omega-conotoxin peptide SNX-111, which selectively blocks depolarization-induced calcium fluxes through neuronal N-type voltage-sensitive calcium channels, protected the pyramidal neurons in the CA1 subfield of the hippocampus from damage caused by transient forebrain ischemia in the rat model of four-vessel occlusion. SNX-111 provided neuroprotection when a single bolus injection was administered intravenously up to 24 hr after the ischemic insult. These results suggest that the window of opportunity for therapeutic intervention after cerebral ischemia may be much longer than previously thought and point to the potential use of omega-conopeptides and their derivatives in the prevention or reduction of neuronal damage resulting from ischemic episodes due to cardiac arrest, head trauma, or stroke. Microdialysis studies showed that SNX-111 was 3 orders of magnitude less potent in blocking potassium-induced glutamate release in the hippocampus than the conopeptide SNX-230, which, in contrast to SNX-111, failed to show any efficacy in the four-vessel occlusion model of ischemia. These results imply that the ability of a conopeptide to block excitatory amino acid release does not correlate with its neuroprotective efficacy.

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Selected References

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