Preventive and therapeutic effects of magnesium sulfate on nikethamide-induced seizures: Implications for COVID-19 treatment

Figure 3 The molecular mechanism of the respiratory rhythm control center in the pre-Bötzinger complex. The 5-hydroxytryptamine (5-HT) is an important neurotransmitter, can activate protein kinase C (PKC) by binding to the 5-HT2A receptor. PKC further regulates the conduction of sodium ions, which is essential for maintaining respiratory rhythm. The activation of N-methyl-D-aspartate receptors (NMDARs) leads to the influx of calcium ions (Ca²⁺) into neurons. Calmodulin is a calcium-binding protein, forms a complex with intracellular Ca²⁺ and further activates nitric oxide (NO) synthase to generate large amounts of NO. Magnesium ions (Mg²⁺) is a natural antagonist of NMDARs, can block Ca²⁺ influx through voltage-gated channels and thus antagonize NMDAR activation. Therefore, Mg²⁺ can be used as an antagonist to treat seizures caused by glutamate. Ca²⁺: Calcium ions; Mg²⁺: Magnesium ions; Na⁺: Sodium ions; NO: Nitric oxide; PKC: Protein kinase C; 5-HT: 5-hydroxytryptamine.