'Magnesium'-the master cation-as a drug-possibilities and evidences

Abstract

Magnesium (Mg²⁺) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions. Magnesium (Mg²⁺) can regulate several cations, including sodium, potassium, and calcium; it consequently maintains physiological functions like impulse conduction, blood pressure, heart rhythm, and muscle contraction. But, it doesn't get much attention in account with its functions, making it a "Forgotten cation". Like other cations, maintenance of the normal physiological level of Mg²⁺ is important. Its deficiency is associated with various diseases, which point out to the importance of Mg²⁺ as a drug. The roles of Mg²⁺ such as natural calcium antagonist, glutamate NMDA receptor blocker, vasodilator, antioxidant and anti-inflammatory agent are responsible for its therapeutic benefits. Various salts of Mg²⁺ are currently in clinical use, but their application is limited. This review collates all the possible mechanisms behind the behavior of magnesium as a drug at different disease conditions with clinical shreds of evidence.

Keywords: Calcium antagonist; Forgotten cation; Hypomagnesemia; Magnesium; NMDA blocker; Vasodilator.

Fig. 1

Physiological roles of magnesium on vital systems. Text in the circle represents the physiological role of Mg in various vital organs. Text in the rectangle indicate the diseases or disorders associated with magnesium deficiency

Fig. 2

Factors associated with magnesium deficiency

Fig. 3

Showing the relationship between excito-toxicity and the beneficial effect of magnesium in it. Excess of calcium influx in brain may cause causes various complication in brain such as excitotoxicity, BBB disruption, inflammation and oxidative stress. Magnesium is found to be beneficial in neurological diseases via correcting the above mentioned complications. i.e., inhibiting calcium influx, substance P production, inflammation and oxidative stress. ROS reactive oxygen species, NMDA receptor N methyl D aspartate receptor, BBB blood brain barrier

Fig. 4

Anti-migraine mechanism of action of magnesium: Migraine is due to mainly three reasons such as platelet activation, CGRP release and cortical spreading depression. Magnesium exhibiting its Antimigraine action through inhibiting platelet aggregation, serotonin release, inhibiting CGRP mediated vasodilation, and inhibiting CSD. 5 HT-serotonin, CGRP calcitonin gene related peptide, NMDA N methyl D aspartic acid receptor, CSD cortical spreading depression

Fig. 5

The beneficial role of magnesium in cardiac tissue

Fig. 6

Showing factors leading to hearing loss and beneficial role of magnesium in it: hearing loss is mainly due to three main reasons; noise induced, drug induced and sudden sensioneural hearing loss. The ionic change associated with hearing loss is corrected by magnesium due to its calcium antagonist action and ischemic related problem are corrected by its vasodilatory property. Excitotoxicity in association with hearing loss is corrected by its non-competitive NMDA antagonist action. Additionally antioxidant action of magnesium is beneficial in oxidative stress and related apoptosis