Papaverine, as the hydrochloride, soluble in alcohol but not readily in water, or the sulphate, soluble in both water and alcohol, is employed locally in 2 to 4 per cent. solution, and by mouth and subcutaneously in dose of 1/2 to 2 grains (0.03-0.12 gm.). Its solutions are unstable and must be kept from the air in alkali-free glass.

Locally

Applied to mucous membranes or injected beneath the skin there is slight irritation, followed by a moderate degree of analgesia and a relaxation of the blood-vessels and tissues of the part.

Central Nervous System

There is a depression of the higher centers like that of morphine, but milder.

Smooth Muscle

There is a relaxation of smooth muscle in stomach, intestines, gall-bladder, bile passages, ureter, bladder, uterus, and the arteries. This is due to a direct effect on the muscle and not through any action on the nervous elements. It is not very constipating.

Heart

Macht found that small doses in a dog caused a slight slowing of the heart and a marked increase in tonicity with increased contractility and increased volume of output. As there is no change if the vagi are cut, or after atropine, or if the accelerator ganglia are destroyed, the action is a direct one on the cardiac muscle. Large doses in the frog caused heart-block and death with the heart in diastole.

Arteries

Owing to depression of muscle it is a powerful dilator of the coronary and systemic arteries with a striking fall in arterial pressure. Pal noted very little effect in normal animals or in those with chronic high blood-pressure, but a striking action after epinephrine or pituitary.

Respiration

The rate is slightly decreased, but the volume output and alveolar ventilation are increased and there is a dilatation of the bronchi. After an intravenous dose the bronchial muscles were relaxed in one minute (Pal).

Elimination

It is eliminated by liver, kidneys and small intestine, mostly unchanged.

Toxicity

Bouchet obtained no striking effect from 15 grains (1 gm.) by mouth. In the frog Macht found the minimum lethal dose 1/1000 of the body weight, in cats 55 mg. per kg. had no effect, and in dogs 50 mg. produced a notable but not serious narcosis.

Therapeutics

It is used: i, to overcome smooth muscle spasm in the viscera, as cardiospasm, pylorospasm, intestinal colic, biliary colic, renal colic, uterine cramps and bronchial asthma. Holzknecht and Saglitzer and others in x-ray work noted that a dose by mouth of 1 grain (0.06 gm.) relaxed the pylorus, and proposed it for the differential diagnosis of pylorospasm from pylorostenosis. Others then employed it in the treatment of pyloric spasm. Hess, in testing three infants with pylorospasm with repeated 1/6 grain (0.01 gm.) doses subcutaneously, found by roentgen rays that it diminished the vomiting and markedly hastened the passage of both small and large bismuth pills through the pylorus, but it delayed their passage through the small intestine.

Macht and Geraghty reported its local value in ureteral stone, and Walther and Fowler each report 3 cases of relief of pain and the passage of the stone after the ureteral instillation of 45 to 75 minims (3-5 c.c.) of a 2 per cent. solution.

2. To overcome vomiting, Pal recommends it in seasickness, and in the hyperemesis of pregnancy and after anesthesia or morphine.

3. To overcome arterial spasm, as in angina pectoris and the arterial crises of arteriosclerosis and tabes. Pal considers it of no value in chronic hypertension cases.

4. To overcome cough, as a substitute for codeine or heroine.