C8H10N4O2,H2O = 212.136.
Synonyms.—Theine, B.P.; Coffeine; Guaranine; Trimethyl-xanthine; Methyl-theobromine.
Caffeine, or trimethyl-xanthine, C5H(CH3)3N4O2,H2O, is an alkaloid contained in the seeds of Coffea arabica, Linn. (N.O. Rubiaceae), in the leaves of Camellia Thea, Link. (N.O. Ternstroemiaceae), in Paullinia Cupana, H.B. and K. (N.O. Sapindaceae), in the seeds of Cola acuminata, Schott and Endl. (N.O. Sterculiaceae), and other species of Cola, and in a few other plants. It is also official in the U.S.P. It may be obtained by treating strong decoctions with lead acetate, which removes tannin, colouring matter, etc., removing excess of lead by means of hydrogen sulphide, filtering, concentrating, and crystallising. Commercially it is prepared chiefly from tea dust or sweepings. It may be obtained synthetically by heating theobromine-silver with methyl iodide. It contains one molecule of water of crystallisation, if crystallised from water; but it is anhydrous when crystallised from alcohol, ether, or chloroform. As found in commerce it usually contains about 7 per cent. of water of crystallisation. The anhydrous substance contains 28.90 per cent. of nitrogen. Caffeine (methyl-theobromine) is trimethyl-xanthine and, like xanthine, the dimethyl-xanthines (theophylline and theobromine), and other members of the same group, may be prepared by synthesis, with urea as a starting point. On heating urea and amino-acetic acid together, uric acid results; oxidising agents convert uric acid into alloxan, and from dimethyl-alloxan it is possible to produce trimethyl uric acid (hydroxycaffeine), from which caffeine can be formed through chlorocaffeine. It occurs in the form of white, odourless, flexible, glistening, silky needles, usually matted together, and having a bitter taste. At ordinary temperatures it gradually loses water of crystallisation, and it becomes anhydrous at 100°. Exposure over sulphuric acid also dehydrates the hydrous alkaloid. Heated at 120° constantly, it loses weight owing to slow volatilisation. It sublimes at 178° and melts at 237° without decomposition. On ignition, it burns with a sooty flame, and leaves no residue. Caffeine is a very feeble base, its salts being decomposed by water. The aqueous solution is neutral to litmus. An acidified aqueous solution yields the whole of its caffeine to benzene, chloroform, or amyl alcohol when either of those solvents is shaken with it. When moistened with strong nitric acid, or dissolved in chlorine water and evaporated on a water-bath, it leaves a reddish-yellow residue which, in contact with ammonia in solution or vapour, becomes purple from formation of murexide, the ammonia salt of purpuric acid. With potassium hydroxide the colour is discharged. The aqueous solution is not precipitated by Mayer's solution (distinction from other alkaloids except theobromine). With solution of silver nitrate it gives a granular crystalline precipitate; and with mercuric chloride, long needles soluble in hydrochloric acid. The salts of the mineral acids have an acid reaction on litmus, and are decomposed by water or alcohol.
Soluble in water (1 in 68), boiling water (1 in 1), alcohol (1 in 40), chloroform (1 in 7), ether (1 in 400), or benzene; its solubility in water is much increased by the addition of sodium benzoate or salicylate.
Action and Uses.—Caffeine exerts three important actions (1) on the central nervous system, (2) on muscle, including cardiac, and (3) on the kidney. The action on the central nervous system is mainly on that part of the brain connected with psychical functions. It produces a condition of wakefulness and increased mental activity. The interpretation of sensory impressions is more perfect and correct, and thought becomes clearer and quicker. With larger doses of caffeine the action extends from the psychical areas to the motor area and to the cord, and the patient becomes at first restless and noisy, and later, may show convulsive movements. Caffeine facilitates the performance of all kinds of physical work, and actually increases the total work which can be obtained from a muscle. On the normal man, however, it is impossible to say how much of the action on the muscle is central and how much peripheral. But, as fatigue shows itself first by an action on the centre, it is probable that the action of caffeine in diminishing fatigue is mainly central. Caffeine accelerates the pulse and slightly raises blood pressure. It has no action in any way resembling digitalis; by increasing the irritability of cardiac muscle its prolonged use rather tends to fatigue than to rest the heart. Caffeine and its allies form a very important group of diuretics. The urine is generally of a lower specific gravity than normal, since it contains a lower proportion of salt and urea; but the total excretion of solids both as regards urea, uric acid, and salts is increased. Caffeine, by exciting the medulla, produces an initial vaso-constriction of the kidneys, which tends at first to retard the flow of urine. So in recent years other drugs have been introduced, allies of caffeine which act on the kidneys in a similar manner, but are without the stimulant action on the brain; theobromine is such a drug. Caffeine has recently been recommended as an antidote to nicotine. A curious property it possesses is that of combining with quinine hydrochloride to form a substance named "basicine," the properties of which differ materially from those of either of its constituents; this compound is soluble in water (1 in 1), and melts at 125°.
Caffeine is employed as a cardiac and renal stimulant in cardiac failure, chronic nephritis and general dropsy, but is contra-indicated in acute renal inflammation. It is of great value in nervous headache and migraine, and is often given with antipyrine or acetanilide. It is frequently effectual in relieving the paroxysms of asthma. A compound of caffeine citrate and antipyrine is sold under the trade-name Migrainine. It contains 9 per cent. of caffeine and is given in doses of 1/2 to 1 gramme (8 to 15 grains). The pure alkaloid is preferred to the citrate for administration in the form of powders, cachets, tablets, and pills, especially if mixed with other ingredients. Pills are best prepared by massing to a crumbling consistence with glycerin of tragacanth and finishing with a trace of syrup of glucose. Caffeine is a constituent of many proprietary headache tablets and cachets (see Pulvis Acetanilidi Compositus). For hypodermic injection, caffeine sodio-benzoate or sodio-salicylate is commonly employed. In cases of poisoning by caffeine, an emetic of mustard, ipecacuanha, or common salt should be administered, followed by the free use of stimulants and the application of warmth to the extremities. Morphine and atropine may be given hypodermically.
Dose.—1/2 to 3 decigrams (1 to 5 grains).
C14H18N4O9 = 386.184.
Caffeine citrate (Caffeina Citrata, U.S.P.; Citrated Caffeine), C8H10N3O2C6H8O7, may be prepared by dissolving 50 parts of citric acid in 100 parts of hot water and dissolving 50 parts of caffeine in the hot solution, evaporating to dryness on a water-bath, with constant stirring towards the end of the operation, and powdering the residue. A simpler method of preparation is to mix the powdered citric acid with the caffeine, damp the mixture with distilled water, and dry. Caffeine citrate is an unstable compound, containing 50.27 per cent. of anhydrous caffeine. It occurs as a white, odourless powder, having a bitter and acid taste, and an acid reaction. The cold saturated solution in absolute alcohol reddens blue litmus only slightly (absence of free citric acid). With 3 parts of water it forms a stiff paste which, if gently warmed, becomes a clear solution; on again cooling it forms an almost solid mass of acicular crystals of caffeine.
Soluble in water (1 in 32), alcohol (1 in 22); and in a mixture of 2 parts of chloroform and 1 part of alcohol (1 in 10).
Action and Uses.—Caffeine citrate is stable in concentrated solutions, but is dissociated on dilution of the liquids, with liberation of the pure alkaloid. Its solutions contain free citric acid, and therefore effervesce with alkali carbonates; it should be prescribed with acids rather than with alkalies. It is incompatible with a mixture of potassium iodide and spirit of nitrous ether, also with antipyrine, sodium salicylate, benzoate, and nitrite. For combination in mixtures with these pure caffeine should be used. Caffeine citrate may be administered in the form of Caffeinae Citras Effervescens, or it may be given enclosed in a cachet.
Dose.—1 to 6 decigrams (2 to 10 grains).
- Caffeinae Citras Effervescens, B.P.—EFFERVESCENT CAFFEINE CITRATE.
- Caffeine citrate, 4; sodium bicarbonate, 51; tartaric acid, 27; citric acid, 18; refined sugar, 14; all in powder. The product should weigh about 100. Dose.—4 to 8 grammes (60 to 120 grains).
- Caffeina Citrata, B.P.C.—CITRATED CAFFEINE.
- Caffeine, 50; citric acid, 50; distilled water, a sufficient quantity. Dose.—1 to 6 decigrams (2 to 10 grains).
- Caffeina Citrata Effervescens, U.S.P.—EFFERVESCENT CITRATED CAFFEINE.
- Citrated caffeine, 4; sodium bicarbonate, dried and powdered, 57; tartaric acid, dried and powdered, 30; citric acid, uneffloresced crystals, 19.5; to make about 100. Average dose.—4 grammes (60 grains).
- Granulae Caffeinae Citratae, B.P.C.—GRANULAR EFFERVESCENT CITRATED CAFFEINE. 1 in 25.
- Dose.—4 to 8 grammes (60 to 120 grains).
- Tabellae Caffeinae B.P.C.—CAFFEINE TABLETS. 1 grain.
The British Pharmaceutical Codex, 1911, was published by direction of the Council of the Pharmaceutical Society of Great Britain.