N-type calcium channels located on presynaptic nerve terminals regulate 
neurotransmitter release, including that from the spinal terminations of primary 
afferent nociceptors. Accordingly, N-type calcium channel blockers may have 
clinical utility as analgesic drugs. A selective N-type calcium channel 
inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a 
novel nonopioid treatment for severe chronic pain. To develop a small-molecule 
N-type calcium channel blocker, the authors developed a 96-well plate 
high-throughput screening scintillation proximity assay (SPA) for N-type calcium 
channel blockers using [125I]-labeled omega-conotoxin GVIA as a channel-specific 
ligand. Assay reagents were handled using Caliper's Allegro automation system, 
and bound ligands were detected using a PerkinElmer TopCount. Using this assay, 
more than 150,000 compounds were screened at 10 microM and approximately 340 
compounds were identified as hits, exhibiting at least 40% inhibition of 
[125I]GVIA binding. This is the 1st demonstration of the use of [125I]-labeled 
peptides with SPA beads to provide a binding assay for the evaluation of ligand 
binding to calcium channels. This assay could be a useful tool for drug 
discovery.