Definition. - Phenyldimethylpyrazolon obtained by the condensation of phenyl-hydrazine with aceto-acetic ether and methylation of the product.

Description and Properties. - A white, crystalline powder, odorless, of a slightly bitter taste, freely soluble in water, alcohol, and chloroform.

Dose. - 3-20 grains (0.19-13.0 Gm.).

Antagonists and Incompatibles. - Antipyrine is incompatible with spirit of nitrous ether and nitrous compounds, the chlorides of mercury, the iodides of arsenic and mercury, the ferric salts in solution, tincture of iodine, most of the vegetable astringents, phenol, chloral, beta-naphthol, sodium bicarbonate, sodium salicylate, and the salts of quinine and caffeine.

Physiological Action. - On the skin it has no action. It irritates mucous membranes and blanches them, and is an analgesic. Hypodermically administered it often forms abscess. Antipyrine is a weak antiseptic.

Digestive System. - Antipyrine being readily soluble, is absorbed rapidly. It is slightly irritant to the stomach, blanches its surface by local contraction of the blood-vessels, and may act as a hemostatic. It hinders the activity of ferments like pepsin and diastase, and may even cause nausea and vomiting. It has little or no action on the intestines, because of its rapid absorption.

Circulation. - In small doses after a preliminary rise in blood-pressure the vessels dilate and the peripheral blood-pressure falls. The central pressure is not much affected. The pulse rate, at first accelerated, becomes slower. The effects of toxic doses is to cause distinct loss of blood and a weak, feeble heart.

Antipyrine has no appreciable action on the blood itself. In this respect it varies greatly from the aniline derivatives, and from this point of view is a much safer analgesic.

Nervous System. - Antipyrine has a pronounced action on the nervous system. It causes irritability of the motor cortex, in lower animals bringing about convulsive seizures. In man it may bring about excitement and a peculiar type of intoxication, accompanied with marked general analgesia. It occasionally interferes with normal intellectual labor. It excites the medulla and then brings about a diminution in its functions and may abolish the spinal reflexes. The cutaneous nerves of sensation are rendered markedly analgesic.

Temperature. - Antipyrine reduces temperature very rapidly in fever. Its action in health is slight. The heat reduction is largely due to increased surface evaporation, from dilated blood-vessels and increase of perspiration. The exact mechanism is not as yet fully understood. A certain proportion of the heat reduction is due to a retardation of metabolism. This is probably not as marked for antipyrine as it is for the quinolines.

Antipyrine is very apt to cause a rash. This rash may resemble the eruption of many eruptive fevers, and hence the use of antipyrine should be withheld in these conditions until a definite diagnosis is made.

Poisoning. - In large doses, 30 grains and over, in some individuals, even in smaller doses, it may bring about a marked feeling of chilliness, dyspnea, vertigo with rapid and feeble heart action, unconsciousness, and collapse. Occasionally, convulsive seizures are noted. Cyanosis is usually present, irregular breathing, even Cheyne-Stokes rhymth; the pulse is small and death may result from cardiac collapse. The temperature usually falls, but often while the patient is in coma there may be a distinct rise in the temperature. 45 grains (3 Gm.) has caused death in a patient with a weak heart. 7 1/2 grains (5 Gm.) has caused serious symptoms. The continuous use of small doses of antipyrine has been known to bring about a tendency to hemorrhages from the mucous membranes.

In large doses it causes slow and irregular breathing.

Absorption and Elimination. - Kidneys. - Antipyrine lessens the amount of urine, urea, and uric acid excreted, but increases the amount of sulphuric acid in the urine.

Therapeutics. - As an analgesic antipyrine probably ranks next to opium, and is useful in all conditions which call for the treatment of pain. The anesthesia produced by antipyrine often lasts for several hours or even days. In acute coryza and inflammation of the pharynx great relief is obtained by spraying the parts with a 2 or 4 per cent. solution, after applying a solution of cocaine to prevent the primary smarting and irritation which the antipyrine produces.

A 20 per cent. solution has been used in otitis, and a 4 per cent. solution has been found very efficient in cystitis.

Antipyrine has been used with some success in diabetes mellitus and malarial diseases, particularly in intermittent fever. It does not, however, possess the antiperiodic and specific action of quinine in malarial poisoning. It is an excellent antispasmodic in whooping-cough, laryngitis, and asthma.

Administration. - The drug is best given in water or some aromatic water or syrup. It should not be given hypodermically. In hemorrhage the powdered drug may be applied locally, or a 40 per cent. solution, which causes less irritation. From 1/2-2 grains (0.03-0.12 Gm.), once or twice a day, is sufficient for children. Ordinarily, a dose of 5 grains (0.3 Gm.) is sufficient for an adult.

Allied Compounds

Antipyrine unites with resorcin to form resopyrin; with salicylic acid to form sali-pyrin; with chloral hydrate to form hypnal and other compounds. Pyramidon is a dimethylamido substitution product of antipyrine. Ferripyrin is a combination of ferric chloride and antipyrine. Many other compounds are known. Antipyrine is a constituent of many "migraine powders."

Dose. - Average dose: 4 grains, (0.250 Gm. = 250 milligrammes), U. S. P.

Caution. - On account of the wide range of incompatibilities already indicated, the greatest caution should be observed in combining antipyrine with other substances.