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Abstract
Ziconotide (PRIALT) is a neuroactive peptide in the final stages of clinical development
as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent
of omega-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism
of action underlying ziconotide's therapeutic profile derives from its potent and
selective blockade of neuronal N-type voltage-sensitive calcium channels (N-VSCCs).
Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including
pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide
from all other analgesics, including opioid analgesics. In fact, ziconotide is potently
anti-nociceptive in animal models of pain in which morphine exhibits poor anti-nociceptive
activity. Moreover, in contrast to opiates, tolerance to ziconotide is not observed.
Clinical studies of ziconotide in more than 2,000 patients reveal important correlations
to ziconotide's non-clinical pharmacology. For example, ziconotide provides significant
pain relief to severe chronic pain sufferers who have failed to obtain relief from
opiate therapy and no evidence of tolerance to ziconotide is seen in these patients.
Contingent on regulatory approval, ziconotide will be the first in a new class of
neurological drugs: the N-type calcium channel blockers, or NCCBs. Its novel mechanism
of action as a non-opioid analgesic suggests ziconotide has the potential to play
a valuable role in treatment regimens for severe chronic pain. If approved for clinical
use, ziconotide will further validate the neuroactive venom peptides as a source of
new and useful medicines.