The drug also worked better with neuropathic and inflammatory pain in animal trials, and tolerance developed more slowly.
A little-known morphinelike drug is potentially more potent, longer lasting and less likely to cause constipation than standard morphine, a study led by a Loyola University Health System anesthesiologist has found.
The drug, morphine-6-0-sulfate, has a similar chemical structure to standard morphine. Loyola University pain expert
Joseph Holtman Jr. MD, PhD, and colleagues* reported in the Dec 2010 issue of the European Journal of Pharmacology(1) that a study they performed in rats "demonstrated potential clinical advantages of morphine-6-0-sulfate compared to morphine."
Opioids, such as morphine, oxycodone and hydrocodone, are standard drugs for treating moderate to severe pain, including cancer pain.
• But these drugs can have significant side effects, including constipation, nausea, vomiting, drowsiness, cognitive dysfunction and slowed breathing and heart rates.
• And while opioids work well for conditions such as back pain and post-operative pain, the drugs are less effective against neuropathic pain, such as tingling, burning or shooting pain.
Constipation is a common side effect of morphine and can be so uncomfortable that some patients limit their use of the drug. Doctors typically do not discharge surgery patients until they have had a bowel movement and this can extend hospital stays.
Holtman and colleagues tested standard morphine and morphine-6-0-sulfate on rats. The animals received the drugs three ways – by mouth, by IV and by injection into the space surrounding the spinal cord.
The rats underwent several well-established tests to determine their sensitivity to pain. In one such test, researchers focused a very warm light beam on the tail and measured how long it took for the rat to flick the tail.
In this tail-flick test, morphine-6-0-sulfate was:
• 10 times more potent than standard morphine when administered in the space surrounding the spinal cord,
• 5 times more potent when administered by IV and
• 2 times more potent when given by mouth.
Morphine-6-0-sulfate maintained its maximum effect for three hours, compared with 1½ hours for standard morphine.
And it took rats 25 days to build tolerance to morphine-6-0-sulfate, compared with 10 days with standard morphine.
Morphine-6-0-sulfate also was more potent than standard morphine for neuropathic and inflammatory pain.
Researchers found that morphine-6-0-sulfate could cause constipation, but only at doses 10 to 20 times higher than the effective doses.
The findings suggest that morphine-6-0-sulfate "may be an interesting potential drug for further study," Dr. Holtman and colleagues wrote.
* The study was conducted at the University of Kentucky, where Dr. Holtman's co-authors all work and where he worked until March 2010. The study was funded by Insys Therapeutic, Inc., which is has a license to develop the drug for possible use in humans.
1. “Antinociceptive effects and toxicity of morphine-6-0-sulfate socidum salt in rat models of pain,” European Journal of Pharmacology, Dec 1, 2010, by Holtman JR Jr., et al.
Source: Loyola University Health System news release, Jan 4, 2011