Take One Snail And Call Me In The Morning...continued
Pain Relief Without Tolerance
Ziconotide causes mental fogginess in some patients, but there is none of the constipation or respiratory suppression seen with morphine, and it is effective against neuropathic pain. Most importantly, there is no tolerance. "We never saw any signs of tolerance in animals or in patients," says Miljanich. "The dose we give in the first week is equally effective a year later."
Tolerance is well understood but difficult to combat. Morphine, for example, turns on a pain-killing process in nerve cells. The body then tries to restore the status-quo, by removing the nerve protein that morphine attaches itself to. Without this on-switch, there is nothing for morphine to latch onto and so no pain killing.
Ziconotide works by turning off the pain signals directly. To combat ziconotide, the body would have to make more and more of the protein that ziconotide turns off, in the hope that it would overwhelm the drug. But, Miljanich says, "there’s a limit to that. There’s only so many calcium channels that a cell can jam into a membrane."
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