QUININE

the most important alkaloid of cinchona bark, used chiefly in the treatment of malaria. During the 300 years between its introduction into Western medicine and World War I, quinine was the only effective remedy for malaria. As a specific treatment for this disease, quinine has benefitted more people than any other drug used thus far to combat infectious diseases. The treatment of malaria with quinine marked the first successful use of a chemical compound in combatting an infectious disease. Like the other cinchona alkaloids, quinine is a large and complex molecule, and its total laboratory synthesis in 1944 is one of the classical achievements of synthetic organic chemistry, although commercial synthesis of quinine is not economically feasible. Quinine acts by interfering with the growth and reproduction of the malarial parasites (Plasmodium species) inhabiting the red cells of the blood; it probably prevents the parasites from oxidizing glucose, their chief source of energy. Administration of quinine dramatically improves the condition of a person suffering from malaria; the parasites promptly disappear from the blood, and the symptoms of the disease are quickly alleviated. When quinine treatment is terminated, however, many recovered patients suffer another attack of malaria several weeks later. This recurrence stems from the failure of quinine to kill the malarial parasites in cells of the body other than the red blood cells. These parasites persist and, after a time, reinvade the red blood cells and precipitate the second malarial attack, or relapse. Because quinine fails to produce a complete cure of malaria, better antimalarial drugs have long been sought. Research during World War II produced a number of antimalarial drugs that almost completely replaced quinine. Some of them, such as chloroquine and chloroguanide, are more effective than quinine in suppressing the growth of the blood forms of the malarial parasite; others, such as primaquine and pyrimethamine, act upon both the blood and tissue stages of the parasite, thus producing complete cures and preventing relapses. All of the newer antimalarials, unlike quinine, may be completely synthesized on a commercial scale. During the 1960s several strains of the malarial parasite Plasmodium falciparum developed resistance to the synthetic drugs, particularly the highly valued chloroquine. The parasite remained sensitive, however, to quinine, which had to be reinstated in various parts of the world as the drug of choice despite the side effects that sometimes occur when the necessarily large doses of quinine are given. In addition to its specific use in malaria, quinine is sometimes used as a nonspecific remedy for fever and pain. It reduces fever probably by dilating the small vessels of the skin; its analgesic (pain-relieving) effect may result from depression of certain centres in the central nervous system. Prolonged administration of quinine may produce toxic symptoms such as deafness, disturbances in vision, skin rashes, and digestive upsets. Some experts believe that patients who undergo quinine treatment may be predisposed to develop blackwater fever, a little understood complication of malaria marked by rapid and severe anemia and the appearance of hemoglobin (the oxygen-carrying blood pigment) in the urine.