Ziconotide is a powerful analgesic drug that has a unique mechanism of action 
involving potent and selective block of N-type calcium channels, which control 
neurotransmission at many synapses. The analgesic efficacy of ziconotide likely 
results from its ability to interrupt pain signaling at the level of the spinal 
cord. Ziconotide is a peptidic drug and has been approved for the treatment of 
severe chronic pain in patients only when administered by the intrathecal route. 
Importantly, prolonged administration of ziconotide does not lead to the 
development of addiction or tolerance. The current review discusses the various 
studies that have addressed the in vitro biochemical and electrophysiological 
actions of ziconotide as well as the numerous pre-clinical studies that were 
conducted to elucidate its antinociceptive mechanism of action in animals. In 
addition, this review considers the pivotal Phase 3 (and other) clinical trials 
that were conducted in support of ziconotide's approval for the treatment of 
severe chronic pain and tries to offer some insights regarding the future 
discovery and development of newer analgesic drugs that would act by a similar 
mechanism to ziconotide but which might offer improved safety, tolerability and 
ease of use.