Antinociceptive effects and toxicity of morphine-6-O-sulfate sodium salt in rat models of pain.

19:48 EDT 2nd September 2015 | BioPortfolio

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 Articles [22643 Associated PubMed Articles listed on BioPortfolio]

Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin.

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, are widely used in the management of different diseases beyond their primary indication for lowering cholesterol. Previo...

Central and peripheral antinociceptive activity of 3-(2-oxopropyl)-3-hydroxy-2-oxindoles.

Convolutamydine A has been shown to develop a significant antinociceptive effect. Here we demonstrated that new analogues (5-iodo-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Iisa), 5-fluoro-3-(2-oxopropyl...

Discriminative stimulus effects of morphine and oxycodone in the absence and presence of acetic acid in male and female C57Bl/6 mice.

The use of prescription opioids for clinical management of pain remains problematic because of concerns about addiction associated with opioid use. Another difficulty in pain management is the increas...

Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy with omega-3 fatty acids.

Recent evidence associates omega-3 fatty acids (O3) with pain reduction. The aim of this work was to evaluate the antinociceptive effect of O3, either alone or in combination with morphine after acute...

On the Effect of Sodium Chloride and Sodium Sulfate on Cold Denaturation.

Both sodium chloride and sodium sulfate are able to stabilize yeast frataxin, causing an overall increase of its thermodynamic stability curve, with a decrease in the cold denaturation temperature and...

Clinical Trials [4036 Associated Clinical Trials listed on BioPortfolio]

Effect of Solar Salt Diet in Elderly Hypertensive Patients

High sodium intake causes hypertension. Various efforts for reducing salt consumption are proceeding all over the world. Solar salt contains reduced sodium and abundant mineral, such as ca...

Bioequivalency Study of Morphine Sulfate Injection, Solution and Tablet Under Fasted Conditions

Determine the pharmacokinetics and optimize study design for subsequent studies with morphine sulfate tablets and solution.

Dose Proportionality and Food Effect of Morphine Sulfate

Establish the dose proportionality of the 15 mg and 30 mg morphine sulfate tablets and to examine the effect of food on absorption from the 30 mg tablet.

Steady State Study of Codeine Sulfate

Study to characterize the steady-state pharmacokinetics of codeine and its metabolites morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) after oral administration of...

Comparative Study to Evaluate KADIAN and Avinza in Healthy Adults

The primary objective of this study was to compare the single-dose relative bioavailability of Alpharma Branded Products Division (Kadian®) and Ligand® Pharmaceuticals Inc. (AVINZA®) 30...

Medical and Biotech [MESH] Definitions

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.

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.

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.

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.

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.


Advertisement
 

Relevant Topics

Nutrition
Latest News Clinical Trials Research Drugs Reports Corporate
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Pain
Latest News Clinical Trials Research Drugs Reports Corporate
Pain is defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Some illnesses can be excruci...

Head and neck cancers
Latest News Clinical Trials Research Drugs Reports Corporate
Cancer can occur in any of the tissues or organs in the head and neck. There are over 30 different places that cancer can develop in the head and neck area. Mouth cancers (oral cancers)  - Mouth cancer can develop on the lip, the tongue, the floor...

Advertisement
 

Searches Linking to this Article