A peptide from a carnivorous cone snail has already led to one pain killer. Researchers suspect that additional analgesics are just waiting to be discovered among the 100,000 other, mostly uncharacterized cone snail peptides.

Marine cone snails, in the genus Conus live in coral reefs surrounding Australia, Indonesia, and the Philippines. There are about 700 species of Conus, each with 100-200 unique peptide molecules in its venom.

Of the few dozen Conus peptides under investigation, each binds selectively and often potently to an ion channel, neurotransmitter receptor, or other cell-surface signaling protein. Researchers suspect that all of the thousands of uncharacterized Conus peptides have similar specificity.

Because pain is initially mediated through signaling proteins at sensory nerve endings, it seems likely that this large collection of novel chemical compounds could lead not only to new analgesics, but also to new ways to study the signaling proteins involved in the perception and transmission of pain.

The first drug from Conus venoms, called Prialt ®, or ziconotide, was approved in 2004 for treating chronic, intractable pain, such as that suffered by people with cancer, AIDS, or certain neurological disorders. It is 1,000 times more powerful than morphine, but is not believed to be addictive.

Prialt blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals. It is delivered directly into fluid surrounding the spinal cord by external or implanted pumps.

Prialt was discovered in 1982 by a recent high school graduate named J. Michael McIntosh who was working in the laboratory of Baldomero Olivera, Ph.D., Distinguished Professor of Biology at the University of Utah.

Now, more than 25 years later, Dr. J. Michael McIntosh, M.D. is a research psychiatrist at the University of Utah. He directs a laboratory that includes several other scientists. His research team, along with research teams in Utah, California, and the Philippines, collaborates with Olivera to study cone snail venom as part of a program project research grant from NIGMS.

This research group identified several other peptides that show pharmaceutical potential and are currently testing them in animals. One peptide, called alpha-conotoxin RgIA, holds particular promise for treating neuropathic pain. The peptide blocks the alpha9alpha10 nicotinic acetylcholine receptor. In doing so, it may reduce inflammation associated with nerve injury and speed recovery from such injury.

The original idea to study the venoms came from Olivera. As a boy, he was intrigued with a particular type of snail, found in his native Philippines, whose sting can kill a person within minutes. Olivera's quest to identify the lethal component in the venom led to the discovery that each snail's venom consists of a cocktail of peptides, each with a powerful and specific effect on the nervous system. Some of the peptides use the same molecular mechanism as the toxins of cobras, scorpions, and Japanese puffer fish. Others have mechanisms all their own.

Thanks to Olivera's academic pursuit of a boyhood fascination, dozens of laboratories worldwide and various pharmaceutical companies now focus their research on cone snail venom. Their work could lead to new drug therapies as well as new research tools to better understand the molecular mechanisms that underlie pain.

To view a lecture by Olivera:
http://ascb.org/ibioseminars/olivera/olivera1.cfm

Link to a longer story about Dr. Olivera and the discovery of Prialt:
http://publications.nigms.nih.gov/findings/sept02/snails.html

Link to a story following the 2004 FDA approval of Prialt:
http://www.nigms.nih.gov/news/results/011205.html

Link to Olivera's cone snail video footage:
http://www.biology.utah.edu/olivera/movies/clownfish/