An Experimental Analgesic Is More Potent Than Morphine

A new study describes morphine-6-0-sulfate, which although having a similar chemical structure to standard morphine, is potentially more potent, longer lasting, and less likely to cause constipation than standard morphine.

Researchers at Loyola University (Chicago, IL, USA) and the University of Kentucky (Lexington, USA) characterized the relatively little-known morphine derivative using a range of well-established rodent pain models, demonstrating that morphine-6-O-sulfate was efficacious using several routes of administration, including neuroaxial (injected into the intrathecal space), parenteral (injection into the peritoneum), and oral administration. The drug showed potent, dose-related, analgesic activities against acute nociceptive pain (using the tail flick test), neuropathic pain (under chronic constriction nerve injury hyperalgesia and allodynia), and inflammatory pain (using the formalin test).

Morphine-6-0-sulfate maintained its maximum effect for three hours, compared with one-and-a-half hours for standard morphine. It also took the rats 25 days to build tolerance to morphine-6-0-sulfate, compared with 10 days with standard morphine. Morphine-6-0-sulfate was also more potent than standard morphine for neuropathic and inflammatory pain. The researchers did find that morphine-6-0-sulfate could cause constipation, but only at doses 10 to 20 times higher than the effective doses. Morphine-6-0-sulfate also had a good separation based on dose (at least 10-fold) between side effects and analgesia in all models of pain tested. In addition, morphine-6-O-sulfate had a more favorable potency ratio for delay of gastrointestinal transit and analgesia, when compared to morphine. The study was published in the December 2010 issue of the European Journal of Pharmacology.

"These preclinical findings suggest that morphine-6-O-sulfate is a potential candidate for development as a novel opioid for management of nociceptive, neuropathic, and mixed pain states,” said lead author Joseph Holtman, MD, PhD, and colleagues of the departments of anesthesiology and molecular pharmacology and therapeutics.

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