[5] Quinine was first isolated in 1820 from the bark of a cinchona tree, which is native to Peru,[5][9][10] and its molecular formula was determined by Adolph Strecker in 1854.

Quinine was frequently prescribed as an off-label treatment for leg cramps at night, but this has become less common since 2010 due to a warning from the US Food and Drug Administration (FDA) that such practice is associated with life-threatening side effects.

[27] Tonic water was initially marketed as a means of delivering quinine to consumers in order to offer anti-malarial protection.

In Italy, the traditional flavoured wine Barolo Chinato is infused with quinine and local herbs, and is served as a digestif.

In Uruguay and Argentina, quinine is an ingredient of a PepsiCo tonic water named Paso de los Toros.

[33][34] Because of the narrow difference between its therapeutic and toxic effects, quinine is a common cause of drug-induced disorders, including thrombocytopenia and thrombotic microangiopathy.

[38] Quinine can cause unpredictable serious and life-threatening blood and cardiovascular reactions including low platelet count and hemolytic–uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), long QT syndrome and other serious cardiac arrhythmias including torsades de pointes, blackwater fever, disseminated intravascular coagulation, leukopenia, and neutropenia.

[5][37] The most common adverse effects involve a group of symptoms called cinchonism, which can include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception.

[5][35][37] More severe cinchonism includes vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in heart rhythms.

Quinine has diverse unwanted interactions with numerous prescription drugs, such as potentiating the anticoagulant effects of warfarin.

Quinine is used for its toxicity to the malarial pathogen, Plasmodium falciparum, by interfering with its ability to dissolve and metabolize hemoglobin.

[44] Since then, several more efficient quinine total syntheses have been achieved,[45] but none of them can compete in economic terms with isolation of the alkaloid from natural sources.

The first synthetic organic dye, mauveine, was discovered by William Henry Perkin in 1856 while he was attempting to synthesize quinine.

The new quinoline heterocycle would then be formed by combining this amine with the aldehyde produced in the tryptamine side-chain cleavage, giving cinchonidinone.

[50]: Table 3B Plate 560  For example, the quinine-catalyzed Michael addition of a malononitrile to α,β-enones gives a high degree of sterechemical control.

[50] Quinine was used as a muscle relaxant by the Quechua people, who are indigenous to Peru, Bolivia and Ecuador, to halt shivering.

[54] A popular story of how it was brought to Europe by the Countess of Chinchon was debunked by medical historian Alec Haggis around 1941.

Most of the Catholic priests trained in Rome had seen malaria patients and were familiar with the shivering brought on by the febrile phase of the disease.

The Jesuit Agostino Salumbrino (1564–1642),[56] an apothecary by training who lived in Lima (now in present-day Peru), observed the Quechua using the bark of the cinchona tree to treat such shivering.

[59] The form of quinine most effective in treating malaria was found by Charles Marie de La Condamine in 1737.

Prior to 1820, the bark was dried, ground to a fine powder, and mixed into a liquid (commonly wine) in order to be drunk.

A historian said, "it was quinine's efficacy that gave colonists fresh opportunities to swarm into the Gold Coast, Nigeria and other parts of west Africa".

In 1865, Manuel Incra Mamani collected seeds from a plant particularly high in quinine and provided them to Charles Ledger.

[66] By the 1930s Dutch plantations in Java were producing 22 million pounds of cinchona bark, or 97% of the world's quinine production.

[66] During World War II, Allied powers were cut off from their supply of quinine when Germany conquered the Netherlands, and Japan controlled the Philippines and Indonesia.

Tens of thousands of US troops in Africa and the South Pacific died of malaria due to the lack of quinine.

[72] Conducting research in central Missouri, John S. Sappington independently developed an anti-malaria pill from quinine.

[74] From 1969 to 1992, the US Food and Drug Administration (FDA) received 157 reports of health problems related to quinine use, including 23 which had resulted in death.

[19][20] Quinine is approved for treatment of malaria, but was also commonly prescribed to treat leg cramps and similar conditions.

[77] For much of the 20th century, women's use of an overdose of quinine to deliberately terminate a pregnancy was a relatively common abortion method in various parts of the world, including China.