The bronchodilator action of khellin.

This paper describes a preliminary investigation into the bronchodilator action of khellin in patients with clinical bronchospasm. Khellin is one of the active principles of the plant Ammi visnaga (Linn.), which grows wild in many eastern Mediterranean countries. Simple decoctions of its seeds have apparently been used by the local native populations for generations as a spasmolytic, in particular for the relief of ureteric colic. The recent interest awakened in its possible therapeutic applications has been largely due to the work of Anrep, Barsoum, Kenawy, and Misrahy (1946, 1947); Anrep, Barsoum, and Kenawy (1949). A number of crystalline substances have been isolated from the seeds (Spath and Gruber, 1938, 1941a and b). Pharmacologically, the most active of these is khellin, which was first isolated by Mustapha in 1879, and chemically is di-methoxy-methylfurano-chromone. Two principal therapeutic properties have been claimed for this substance. It is said to dilate the coronary arteries and to relax smooth muscle throughout the body, including that of the bronchi. Anrep and others, working on guinea-pig lungs, showed that khellin was a bronchodilator with an activity four to six times greater than that of theophylline-with-ethylenediamine. Weight for weight, however, it was considerably weaker than adrenaline, 4 jmg. of khellin being approximately equivalent to 0.01 ,ug. of adrenaline. They found the drug to be rapidly absorbed by the intramuscular or oral route and stated that its rate of excretion or destruction in the body is slow, so that with continued administration it tends to be cumulative. Kenawy, Barsoum, and Bagoury (1950) have reported favourably on the treatment of bronchial asthma with khellin, and Rosenman, Fishman, Kaplan, Levin, and Katz (1950) have described good results in the treatment of chronic cor pulmonale. We were encouraged to begin this investigation by the dramatic improvement observed in a case with severe clinical bronchospasm, following the oral administration of khellin.* The patient, a man aged 58 years, had been in hospital under the care of one of us for three months with severe continuous asthma, unresponsive to any of the usual remedies. He remained persistently orthopnoeic, wheezing, cyanosed, and distressed, and required oxygen almost continuously. Twenty-four hours after beginning oral khellin, 50 mg. thrice daily, his dyspnoea, orthopnoea, and wheezing disappeared and he lay flat for the first time for many months.