What is the mechanism of action of antimalarials?
The precise MOA is unknown. Antimalarials are weak bases and accumulate in acidic vesicles such as lysosomes. By increasing lysosomal pH, there is a disruption in the normal assimilation of peptides with class II major histocompatibility complex molecules or binding of RNA/DNA to toll-like receptors (especially TLR7, TLR9). Antimalarials have also been shown to decrease production of interleukin-1 (IL-1), IL-6, interferons, and prostaglandins by cells.
Other cellular effects of antimalarials are beneficial. For instance, they can increase lipoprotein (low-density lipoprotein) receptors, thus helping to lower lipid levels. They also decrease insulin degradation, helping to prevent diabetes mellitus. Finally, they can inhibit platelet aggregation and adhesion, helping to prevent thrombosis.