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).
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 ]
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:
Prialt Fact Sheet from Elan: