Antinociceptive effects and toxicity of morphine-6-O-sulfate sodium salt in rat models of pain.
Summary of "Antinociceptive effects and toxicity of morphine-6-O-sulfate sodium salt in rat models of pain."
Mu-opioids (i.e. morphine, oxycodone, hydrocodone) are considered to be the primary drugs for treatment of moderate to severe acute, chronic and cancer pain. Despite their analgesic effectiveness they have several clinically significant side-effects (cognitive, motor, respiratory, cardiovascular, gastrointestinal). They also have a limited spectrum of action, being more effective for nociceptive than neuropathic pain. In an effort to identify other opioid analgesics with greater effectiveness in mixed pain states and with a better side-effect profile compared to the classical mu-opioid agonist, morphine, a relatively little-known morphine derivative, morphine-6-O-sulfate, was characterized using a range of well-established rodent pain models. The present data demonstrated that morphine-6-O-sulfate was efficacious after several routes of administration, including neuroaxial (intrathecal), parenteral (intraperitoneal) and oral in the rat. It showed potent, dose-related, analgesic activities against acute nociceptive pain (the tail flick test), neuropathic pain (chronic constriction nerve injury hyperalgesia and allodynia) and inflammatory pain (formalin test). It had a good separation based on dose (at least 10-fold) between side-effects (incoordination, hypolocomotion, inhibition of gastrointestinal motility) 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. 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.
Affiliation
Anesthesiology, College of Medicine, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0293, USA; Pharmaceutical Science, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536-0082, USA.
Journal Details
This article was published in the following journal.
Name: European journal of pharmacology
ISSN: 1879-0712
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20828549
- DOI: http://dx.doi.org/10.1016/j.ejphar.2010.08.034
Medical and Biotech [MESH] Definitions
Estrogens, Conjugated (usp)
A pharmaceutical preparation containing a mixture of water-soluble, conjugated estrogens derived wholly or in part from URINE of pregnant mares or synthetically from ESTRONE and EQUILIN. It contains a sodium-salt mixture of estrone sulfate (52-62%) and equilin sulfate (22-30%) with a total of the two between 80-88%. Other concomitant conjugates include 17-alpha-dihydroequilin, 17-alpha-estradiol, and 17-beta-dihydroequilin. The potency of the preparation is expressed in terms of an equivalent quantity of sodium estrone sulfate.
Morphine
The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
Sodium Acetate
The trihydrate sodium salt of acetic acid, which is used as a source of sodium ions in solutions for dialysis and as a systemic and urinary alkalizer, diuretic, and expectorant.
Copper Sulfate
A sulfate salt of copper. It is a potent emetic and is used as an antidote for poisoning by phosphorus. It also can be used to prevent the growth of algae.
Taurodeoxycholic Acid
A bile salt formed in the liver by conjugation of deoxycholate with taurine, usually as the sodium salt. It is used as a cholagogue and choleretic, also industrially as a fat emulsifier.
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