Related entry: Red Cinchona Bark
C20H24N2O2, 3H2O = 378.26.
Quinine, C20H24N2O2, 3H2O, is the chief alkaloid of Cinchona Calisaya, Weddell, and other trees of the N.O. Rubiaceae, more especially C. Ledgeriana, Moens, and C. lancifolia, Mutis. It is official in the U.S.P. It may be obtained from the powdered bark, in which it doubtless pre-exists in combination with quinic or cinchotannic acid, by mixing the powder with lime, and extracting with alcohol or petroleum spirit; or by repeatedly boiling the bark with diluted sulphuric or hydrochloric acid, and precipitating the solution with solution of ammonia. The precipitate thus obtained is dissolved in 75 or 80 per cent. alcohol, neutralised with diluted sulphuric acid, and the alcohol distilled off. The resulting quinine sulphate on crystallising is separated from the mother-liquor, and repeatedly re-crystallised from water, whereby the salt is completely freed from the sulphates of the other alkaloids. The solution of the quinine sulphate in diluted sulphuric acid is precipitated by ammonia, the curdy precipitate of the alkaloid first formed being amorphous and anhydrous, but subsequently changing in presence of ammonia and water into a minutely crystalline state with three molecules of water. It is washed and dried at a low temperature. Quinine is considered to be a derivative of hydro-diquinoline. It occurs as a white, soft, flaky, or granular powder, or as a micro-crystalline powder consisting of minute four-sided prisms terminated by pyramids, sometimes slightly damp from adhering moisture, odourless, and having a bitter taste, slightly efflorescent in dry air. Its aqueous solution is laevorotatory, and is alkaline to litmus, but not to phenolphthalein. Its solution in diluted sulphuric acid has a strong blue fluorescence, perceptible 1 in 200,000, which is destroyed by the halogen acids, hyposulphites, and other substances. Quinine is a strong base with an alkaline reaction in aqueous and alcoholic solutions, neutralising the strongest acids, forming neutral and acid salts, which for the most part crystallise well, their solutions tasting intensely bitter. At ordinary temperatures it gradually loses its water of crystallisation—the 3H2O corresponding to 14 per cent.; it also becomes anhydrous on standing over sulphuric acid. On heating, it fuses at 57°, loses two molecules of water of crystallisation at 100°, and becomes anhydrous at 125°, in which condition it melts at about 174°. On evaporating a chloroformic solution, and drying the residue at 100°, the anhydrous base is obtained. On ignition, it leaves no residue. Quinine reacts with the usual alkaloidal reagents. It should dissolve in concentrated sulphuric acid without imparting more than a faint yellowish tint (absence of readily carbonisable impurities); treatment with nitric acid should not produce a red colour (distinction from morphine). In a slightly warmed mixture of 6 mils of absolute alcohol and 3 mils of ether, 1 gramme of the alkaloid should dissolve completely and should remain clear on cooling (absence of cinchonine and cinchonidine). The addition of 2 or 3 mils of solution of bromine, followed by 1 mil of solution of ammonia to 1 mil of a 1 per cent. aqueous solution, containing sufficient sulphuric acid to dissolve the base, produces an emerald-green colour (thalleioquin reaction). If 7 decigrams be dissolved in a mixture of 15 mils of acetic acid, 6 mils of alcohol, and 5 decimils (0.5 milliliters) of sulphuric acid, the solution heated to boiling, and 7 mils of a saturated solution of iodine in alcohol be added slowly, bronze or olive-green crystals of quinine iodo-sulphate will separate on gradually cooling the solution (Herapath reaction); the crystals formed are insoluble in cold water. Quinine should be free from ammonia, and on heating to 125° should not lose more than 14.3 per cent. of its weight (absence of excess of water). On heating with glycerin to about 180° it is converted into the isomeric base quinicine, which is amorphous and dextrorotatory.
Slightly soluble in water, soluble in alcohol (1 in 1), ether (1 in 4), chloroform (1 in 3), in carbon bisulphide, benzene, volatile and fixed oils, diluted acids, solution of ammonia, and to some extent in glycerin.
Action and Uses.—Quinine is a general protoplasmic poison, and in sufficient concentration paralyses all forms of living matter. It is especially fatal to undifferentiated protoplasm; fresh-water amoebae are rendered motionless by a solution of 1 in 50,000 quinine, and stronger solutions rapidly disintegrate these unicellular organisms. The movements of cilia and spermatozoa are likewise brought to a standstill, and the latter finally destroyed. Quinine, therefore, exerts an antiseptic action; it prevents acetic and butyric fermentation, and inhibits the growth of yeast and putrefying organisms. It also retards the action of many unorganised ferments, especially pepsin and trypsin, and to some extent pytalin and diastase. It inhibits the action of oxydases, and to this property is attributed the remarkable power of quinine to diminish metabolism. The absorption of food is not affected, but the solids of the urine, and especially its nitrogenous constituents, are greatly reduced. Though protein metabolism is thus diminished, the absorption of oxygen and the elimination of carbonic acid are unaffected; there is therefore assumed to be a conservation in the body of nitrogenous material, which in the ordinary course would have been oxidised, appearing in the solids of the urine. Quinine, after absorption, exercises upon the white corpuscles of the blood an effect exactly similar to that exerted upon fresh-water amoebae; it tends to arrest their amoeboid movements so that diapedesis becomes impossible. The use of the drug therefore tends to inhibit the formation of pus, but large doses are necessary to prevent suppuration. This alkaloid may also be used in any disease due to protozoa; thus, it has been used with some success in the treatment of syphilis. Quinine has long been supposed to exert an action on the uterus, and it is true that large doses will slightly increase uterine peristalsis, but it can hardly be classified with the group of emmenagogues and abortifacients. The action of quinine on leucocytes is only an example of its effects on the tissues generally. Quinine is a specific in malaria, its action on the malarial parasite being another example of its general effect as a protoplasmic poison. On the warm stage of a microscope, the movements of the protozoon of malaria are arrested by a solution of quinine (1 in 10,000); the organism is, however, more susceptible to the action of quinine at some stages of its existence than at others, and the best results are obtained by the administration of the dose a few hours before the paroxysm, so that, allowing time for absorption, the quinine may be in greatest concentration in the blood at the time of the breaking up of the segmented organism into spores, which is coincident with the onset of fever. Quinine is sometimes used in fevers as an antipyretic; its action in reducing temperature is due to diminished hear production, not to augmented loss of treat. In acute fevers the lessened tissue destruction following the use of quinine is probably as important as the reduction of temperature. Many persons show a marked idiosyncrasy to quinine, and comparatively small closes may produce symptoms of "quinism," including giddiness, headache, humming noises in the ears, with deafness that may last a few hours, disturbances of vision, and sometimes erythematous or urticarial skin eruptions. Quinine is employed in headache and neuralgia, hay fevers, and influenzal catarrhs, usually in the form of the sulphate, hydrochloride, or hydrobromide. The pure alkaloid is rarely employed. On account of its comparative insolubility in water pure quinine is almost tasteless, and may be conveniently swallowed with milk.
Dose.—½ to 3 decigrams (1 to 5 grains).
- Oleatum Quininae, U.S.P.—Same as Oleinatum Quininae, B.P.C.
- Oleinatum Quininae, B.P.C.—OLEINATE OF QUININE. Syn.—Oleatum Quininae, Oleate of Quinine.
- Quinine, 25; oleic acid, by weight, 7.5. Readily absorbed by the skin; it is sometimes mixed with cod-liver oil, in the proportion of 5 decigrams to 30 mils (8 grains to 1 fluid ounce) for application, prior to treatment by X-rays.
The British Pharmaceutical Codex, 1911, was published by direction of the Council of the Pharmaceutical Society of Great Britain.