Accumulation of calcium following experimental traumatic brain injury (TBI) has 
been demonstrated to be a prominent pathophysiological component that can 
compromise mitochondrial functioning and threaten cell survival. The 
omega-conopeptide SNX-111, also known as Ziconotide, is a potent antagonist of 
the voltage-gated N-type calcium channel and has demonstrated significant 
neuroprotective effects against ischemia-induced neuronal injury. To determine 
whether this compound would be effective in reducing calcium accumulation 
associated with TBI, SNX-111 was administered intravenously to rats 1 hour 
following a moderate (2.2 to 2.75 atm) lateral fluid-percussion injury (or sham) 
at doses of 1 (n = 30), 3 (n = 31), or 5 (n = 30) mg/kg; another group received 
0.9% saline solution (n = 35). Brains were processed for calcium 45 (45Ca) 
autoradiography at 6, 12, 24, 48, and 96 hours following insult. Optical density 
measurements of 20 cortical and subcortical regions were analyzed. Injured 
animals administered saline solution exhibited a significant increase in 45Ca 
uptake within 12 regions ipsilateral to the site of injury. The most prominent 
increases were evident throughout the ipsilateral cerebral cortex. SNX-111 
reduced the injury-induced calcium accumulation within the ipsilateral cortex in 
a dose-response fashion when measured at 6, 12, and 48 hours after insult. These 
drug-induced reductions in calcium accumulation were as high as 75% in the 
ipsilateral cerebral cortex, and up to 50% in other ipsilateral regions 
(including thalamus and hippocampus). Consequently, the results suggest that 
posttraumatic blocking of the voltage-gated N-type calcium channel after injury 
reduces prolonged, trauma-induced calcium accumulation.