Ziconotide is a novel peptide that blocks the entry of calcium into neuronal 
N-type voltage-sensitive calcium channels, preventing the conduction of nerve 
signals. N-type calcium channels are present in the superficial laminae of the 
dorsal horn of the spinal cord. In various animal models of pain, intrathecal 
administration of ziconotide blocked nerve transmission and nociception. The 
United States Food and Drug Administration recently approved ziconotide 
intrathecal infusion for the management of severe chronic pain in patients who 
require intrathecal therapy and who are intolerant of or refractory to other 
treatment, such as systemic analgesics, adjunctive therapies, or intrathecal 
morphine. The drug has a narrow therapeutic window and a lag time for the onset 
and offset of analgesia and adverse events. In early clinical trials, frequent 
and severe psychiatric and central nervous system adverse effects were 
associated with rapid intrathecal infusion (0.4 microg/hr) and frequent 
up-titration (every 12 hrs). Therefore, patients with psychiatric symptoms are 
not candidates for this drug. Drug trials of external intrathecal catheters and 
microinfusion devices demonstrated a 3% risk of meningitis. A low initial 
infusion rate of 0.1 microg/hour and limiting infusion rate increases to 2-3 
times/week are now recommended. Patients responsive to intrathecal ziconotide 
require an implanted infusion system to receive long-term therapy.