Micronized Organic Magnesium Salts Enhance Opioid Analgesia in Rats

Abstract

PurposeAs previously reported, magnesium sulphate administered parenterally significantly increased an opioid antinociception in different kinds of pain. Since the typical form of magnesium salts are poorly and slowly absorbed from the gastrointestinal tract we examined whether their micronized form could increase opioids induced antinociception.MethodsIn behavioural studies on rats morphine, tramadol and oxycodone together with magnesium (lactate dihydrate, hydroaspartate, chloride) in micronized (particles of size D90 < 50 μm) and conventional forms were used. Changes in pain thresholds were determined using mechanical stimuli. The intestinal absorption of two forms of magnesium lactate dihydrate (at the doses of 7.5 or 15 mg ions) in the porcine gut sac model were also compared.ResultsMicronized form of magnesium lactate dihydrate or hydroaspartate but not chloride (15 mg of magnesium ions kg-1) enhanced the analgesic activity of orally administered opioids, significantly faster and more effective in comparison to the conventional form of magnesium salts (about 40% for oxycodone administered together with a micronized form of magnesium hydroaspartate). Moreover, in vitro studies of transport across porcine intestines of magnesium ions showed that magnesium salts administered in micronized form were absorbed from the intestines to a greater extent than the normal form of magnesium salts.ConclusionsThe co-administration of micronized magnesium organic salts with opioids increased their synergetic analgesic effect. This may suggest an innovative approach to the treatment of pain in clinical practice.

Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

“…It is worth noting that magnesium ions [Mg 2+ ] belong to the class of physiological antagonists of NMDA receptors [3,4]. Results of own studies and the literature data demonstrated that Mg 2+ increased opioid analgesia in experimental animal models of neuropathic [5][6][7], inflammatory [5], as well as acute [8][9][10] pain. Furthermore, the results of several clinical trials confirmed that parenterally administered Mg 2+ reduces opioid consumption and improves postoperative pain scores without increasing opioid side effects [11][12][13][14].…”

Dietary Magnesium Supplements – Is there any Problem?

“…Today optimalized dosage forms in comparison to old standard ones can even double the bioavailability of a certain compound [61,62]. Or micronization, for example, can also dramatically improve the absorption [63].…”