find the parasite is not resistant. Sertraline, fluoxetine and paroxetine reverse chloroquine resistance, making resistant biotypes susceptible if used in a cotreatment. Antiviral Chloroquine has antiviral effects against some viruses. It increases late endosomal and lysosomal pH, resulting in impaired release of the virus from the endosome or lysosome – release of the virus requires a low pH. The virus is therefore unable to release its genetic material into the cell and replicate. Chloroquine also seems to act as a zinc ionophore that allows extracellular zinc to enter the cell and inhibit viral RNA-dependent RNA polymerase. Other Chloroquine inhibits thiamine uptake. It acts specifically on the transporter SLC19A3. Against rheumatoid arthritis, it operates by inhibiting lymphocyte proliferation, phospholipase A2, antigen presentation in dendritic cells, release of enzymes from lysosomes, release of reactive oxygen species from macrophages, and production of IL-1. History In Peru, the indigenous people extracted the bark of the Cinchona tree (Cinchona officinalis) and used the extract to fight chills and fever in the seventeenth century. In 1633 this herbal medicine was introduced in Europe, where it was given the same use and also began to be used against malaria. The quinoline antimalarial drug quinine was isolated from the extract in 1820. After World War I, the German government sought alternatives to quinine. Chloroquine, a synthetic analogue with the same mechanism of action was discovered in 1934, by Hans Andersag and coworkers at the Bayer laboratories, who named it Resochin. It was ignored for a decade, because it was considered too toxic for human use. Instead, in World War II, the German Africa Corps used the chloroquine analogue 3-methyl-chloroquine, known as Sontochin. After Allied forces arrived in Tunis, Sontochin fell into the hands of Americans, who sent the material back to the United States for analysis, leading to renewed interest in chloroquine. United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug. It was introduced into clinical practice in 1947 for the prophylactic treatment of malaria. Chemical synthesis The first synthesis of chloroquine was disclosed in a patent filed by IG Farben in 1937. In the final step, 4,7-dichloroquinoline was reacted with 1-diethylamino-4-aminopentane. By 1949, chloroquine manufacturing processes had been established to allow its widespread use. Society and culture Formulations Chloroquine comes in tablet form as the phosphate, sulfate, and hydrochloride salts. Chloroquine is usually dispensed