C8H10N4O2, H3C6H5O7. A weak compound of caffeine and citric acid.

Characters. - A white inodorous powder with an acid and faintly bitter taste and an acid reaction on litmus.

Preparation. - Dissolve citric acid (1) in hot water (2), add caffeine (1),. evaporate to dryness, and reduce to a fine powder.

Solubility. - It is soluble in a mixture of two parts of chloroform and one part of rectified spirit.

Reactions. - With a little water it forms a clear syrupy solution, which on dilution yields a white precipitate of caffeine that redissolves when ten parts of water have been added.

Dose. - 1 to 5 grains. Caffeine is very soluble in solutions of benzoate, cinnamate, or salicylate of sodium. By using these as solvents concentrated solutions of caffeine can be made for hypodermic injection. Caffeine 20 gr., salicylate of sodium 17 1/2 gr., gr., water 1 fl. dr. makes a non-irritating solution containing 1 gr. of caffeine in 3 min., but stronger solutions may be made if required.

Action. - Caffeine causes at first stimulation and subsequently paralysis of nerve-centres in the cerebrum, cord, and medulla. It has also a marked action on muscular fibre, both voluntary and involuntary. In large doses it acts as a gastro-intestinal irritant. Its action on frogs varies according to the species. In rana temporaria it produces a rigid condition of the muscles resembling rigor mortis, especially when locally applied to them. In rana esculenta this action on the muscles is slight, and the chief symptom is tetanus, which, like that of strychnine, depends on the action of the drug on the spinal cord. This is followed by paralysis (of voluntary movement) and then of reflex action. The action of theine is said by Mays to differ from that of caffeine; it affects in the frog chiefly sensation, which it paralyses, and causes tetanus, while caffeine does not.1 In warmblooded animals also caffeine (? theine) produces tetanic convulsions, which may be arrested by artificial respiration, and death frequently prevented even from a very large dose. Morphine lessens the convulsions but does not prevent death.

From its stimulant action on the brain, doses of 2-8 grains sometimes cause heaviness of the head, flashes of light before the eyes, singing in the ears, loss of sleep, great restlessness, and delirium.

Its stimulant action on the medulla and cardiac centres increases the respiration and pulse-rate and raises the blood-pressure in moderate doses. Large doses depress the respiration and pulse, and lower the blood-pressure. In man the pulse, after somewhat large doses, becomes very frequent, irregular, and intermittent. This effect occurs in some persons even after a single cup of coffee, but it is prevented in such cases by adding a little brandy to the coffee, as is usually done when coffee is taken without milk.

It appears sometimes to increase the salivary secretion. It has little action on the peristaltic movements of the intestine,

1 Mays, Therapeutic Gazette, 1886, p. 587. Mays states that, commercially, theine and caffeine are considered identical, so that a specimen of so-called 'caffeine' may really be theine, or a mixture of the two alkaloids (op. cit.).

but it causes the intestinal veins to become much dilated, and appears to cause haemorrhoids.

The temperature is not altered by small doses of caffeine, but is increased by large doses.

Caffeine acts as a diuretic, though not invariably so. Its diuretic action may partly depend upon its stimulant action on the heart and vaso-motor centre, and consequent rise of blood-pressure, but the contraction of vessels may be so great that no diuresis takes place till the renal nerves are divided (p. 432). This diuretic action is also due in part to a stimulant action on the cells of the urinary tubules, as Brackenridge, Schroder, and others have shown that it increases the excretion of urinary solids as well as the amount of water.

Uses. - It is used in headache, especially migraine and in cases where the headache seems to be inside the head without any external tenderness. As a diuretic it is especially useful in cardiac dropsy, though it may be given also in cases of hepatic dropsy. It acts as a diuretic even when the kidneys are diseased, and is useful even in very advanced cardiac cases. It is best given alternately with digitalis or along with it.