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

• DOI: 10.1073/pnas.90.16.7894
• Publication Date: 2006-05-31T12:28:51Z
• Authors: K Valentino; R Newcomb; T Gadbois; T Singh; S Bowersox; S Bitner; A Justice; D Yamashiro; B B Hoffman; R Ciaranello
• Keywords: Sodium channel blocker; Brain ischemia

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