ZICONOTIDE (Prialt®, SNX 111)

Molecular Weight: 2639.16 g/mol
Molecular Formula: C₁₀H₁₇₂N₃₆O₃₂S₇

Source: Derivative of a conotoxide of cone snails Conus geographicus, Conus magus (MOLLUSCA).
Activity: Analgesic
Status: FDA-Approved Dec. 2004 for the management of severe pain (see below)

Ziconotide is a synthetic derivative of short (25 amino acid) peptide extracted from the venom of predatory cone snails (Conus geographicus, Conus magus). This drug, a member of a newly described chemical family called the conopeptides, is a generating a lot of interest as a potential pain management drug.

Results from clinical trials to date have suggested ziconotide's effectiveness in treating pain may be from fifty to several thousand times better than that of morphine. It is non-addictive and thus may be suitable for long-term use if it also proves to be non-damaging (but see below). Cancer and AIDS patients and people suffering from chronic neuropathic pain are the initial target patients for the drug. Ziconotide is also reportedly being administered intravenously in some surgery patients.

Ziconotide appears to suppress pain by targeting and blocking specific neuron presynaptic ion channels (called N-type calcium channels) to short-circuit neurotransmitter release in nerves that transmit pain signals. The precisely targeted mode of action effectively blocks pain while still allowing the rest of the nervous system to function properly. This represents an important advantage of this drug over that of currently available opiates with more systemically suppressive effects (e.g. sedation, respiratory depression, etc.).

The fact that ziconotide and other conotoxins are short (usually 20-30 amino acids) means that synthetic derivatives are typically easy to produce. The potential risk of neurotoxicity is being evaluated but the drug has been conditionally approved for use as the significant benefits of this powerful drug outweigh the risk.

A synthetic version of the drug, SNX-111, is manufactured by licensee Elan Corporation under the trade name Prialt®. The drug achieved its primary endpoint in Phase III clinical trials in January 2003, and was approved in late 2004 in the US and early 2005 in the EU for the management of chronic pain in patients for whom intrathecal therapy (e.g., by means of an implanted infusion pump) is warranted, and who are intolerant of or resistant to other treatment.

A similar synthetic conopeptide called AM336 31 has also been recently reported. This compound has also very recently been put into clinical trials. A natural conotoxin called ACV1, isolated from Australian C. victoriae, has also recently been placed into early clinical trials as a treatment for neuropathic pain associated with diabetes.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Kijjoa A and P Sawangwong. 2004. Drugs and cosmetics from the sea (review paper). Mar. Drugs 2004:73-82.

University of Edinburgh cone snail and conotoxin information page:
http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group13/snails.html

chronicpainfoundation.org:
http://www.chronicpainfoundation.org/home/index.php?module=articles&EntryID=8

medicalnewstoday.com:
http://www.medicalnewstoday.com/medicalnews.php?newsid=10071

Prialt Fact Sheet from Elan:
http://www.elan.com/research_development/prialt