Ziconotide: a review of its pharmacology and use in the treatment of pain

Abstract

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.

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

“…NVDCCs regulate presynaptic release of transmitters at many synapses (Snutch, 2005). The NVDCC blocker ziconotide is a powerful analgesic drug approved for the treatment of severe chronic pain in humans (McGivern 2007), and other NVDCC blockers are being developed for use in humans to treat stroke and pain (Giordanetto et al, 2011). Such blockers might also help treat addiction, since rodent studies have shown that NVDCCs promote alcohol intake (Newton et al, 2004) and that NDVCC blockers are antinociceptive, potentiate morphine analgesia, and attenuate morphine tolerance and physical dependence and withdrawal (Meng et al, 2008).…”

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

“…Indeed, inhibition of CaV2.2 by synthetic conopeptides provides analgesic relief in a variety of platforms (3)(4)(5)(6). However, given the importance of CaV2.2 integrity in peripheral and central synapses, directly targeting channel function is complicated by a myriad of adverse side effects (7)(8)(9). Targeting protein-protein interactions that regulate CaV2.2 may provide analgesic benefits similar to those provided by direct inhibition, while avoiding complications associated with channel block.…”

Dynorphin a Analogs for the Treatment of Chronic Neuropathic Pain

“…Ziconotide, a natural peptide from snail venom, is approved for the treatment of intractable chronic pain [8,9]. Ziconotide administration is limited to intrathecal because of cardiovascular liabilities caused by the intravenous route [10]. There appears to be many treatments for neuropathic pain, but most of them are not effective in some patients showing high numbers needed to treat (NNT) and/or develop serious side effects (Table 1).…”