Magnesium deficiency increases ketamine sensitivity in rats

Abstract

Magnesium deficiency increases ketamine sensitivity in ratsPurpose: Inhibition of the NMDA receptor likely contributes to ketamine's neurodepressive properties, Magnesium also inhibits the NMDA receptor by binding to a site associated with the ketamine-binding domain. Electrophysiological studies suggest that magnesium prevents ketamine from binding to the NMDA receptor and thereby prevents ketarnine inhibition. We undertook an in v/vo study to determine if magnesium defK:iency was associated with an increased sensitivity to ketamine. Methods: Weanling rats were maintained on a Ng2+-deficient or control diet for 14 days, In Study I, rats were anaesthetized then sacrificed and the Mg 2+ concentrations in the brain and plasma were measured. In a second prospective study, experimental animals were rendered hypomagnesaernic and the potency of 125 rng.kg -~/p ketamine was evaluated. Animals were then were fed a Mg 2 § diet and ketarnine sensitivity was re-examined 14 days later. R~ults: The Mg2 § diets rendered the rats hypornagnesaemic as indicated by the brain and plasma concentration of Mg 2+, In Study 2, the time to loss of fighting reflex was shorter: 1.9 4-0.3 rnin (n = 12) and 2.6 4-0.2 rnin (n = 16, P < 0.05), whereas the latency to toe pinch was prolonged: 25.0 -5.8 rnin (n= 12) vs 3. I +-2. I rnin (n = 16, P < 0.05) in the Mg2+-delicient compared with age-matched control animals, respectively. The hypornagnesaemic animals had a higher death rate following ketamine injec'don. The increased sensitivity to ketamine was no longer apparent when the animals were re-tested following replenishment of Mg 2+. Conclusion: Hypornagnesaemia is associated with an increased sensitivity to ketamine.

Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with the AMPA/BDNF pathway

“…This effect was associated with the phosphorylation of mTOR and an increased BDNF level in the hippocampus (Akinfiresoye and Tizabi 2013 ). It appears that despite the similar binding sites of ketamine and magnesium on NMDARs, different affinities of magnesium and ketamine to the NMDARs and differences in the pharmacokinetic profiles are the main factors that differentiate the onset of action and the profile of the antidepressant-like activity of these compounds (Orser et al 1997 ).…”

Magnesium: physiology and pharmacology

“…29 It has also been demonstrated that magnesium deficiency increases ketamine sensitivity in rats, both agents probably exerting their effects via NMDA receptor antagonism. 132…”

The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review

“…86 Hypomagnesemia increased ketamine sensitivity in a rat Mg deficiency model. 87 NMDA receptors are important components of pain processing, and their response can be inhibited by ketamine and Mg, which have a super-additive effect in combination. This may explain in part why analgesia is more effective for the combination than for either compound alone.…”