Scillarenin Rhamnose-Glucose Scillarenin A Chemical Structure

Scillaren was made by Sandoz

Scillaren N.N.R. is a mixture of the natural glycosides, scillaren-A and scillaren-B, occurring in fresh squill, Urginea maritima, in the proportions in which they exist in the fresh crude drug, i. e., about 2 parts of scillaren-A to 1 part of scillaren-B. It occurs as a white or yellowish white, odorless, granular powder, possessing a very bitter taste; it is soluble in absolute alcohol (1:5) and sparingly soluble in water (1:3,000).

Extensive attempts by early workers to isolate the native glycosides of squill resulted only in purified extracts. Thus, the scillipicrin, scillitoxin and scillin of Merk,32 1879; the scillain of von Jarmersted;33 the apparently crystalline substances, scilli-picrin, scillenin and scillimarin, of Waliszewski,34 1894 and the substances, scillitin and scilli diuretin, by Kopaczewski,35 1914, were not characterized as pure compounds. Furthermore, the three earlier workers failed to make definite statements concerning their physiologic activity. The successful isolation of the genuine, active, pure cardio-active principles of fresh squill was accomplished by A. Stoll26 and his co-workers, in 1933 and 1935, after extensive investigations. His work was assisted by the discovery that the toxicity of the preparations ran parallel to the intensity of the so-called Liebermann's cholesterol reaction. Active and partially purified extracts of squill first show a strong red color, which changes rapidly to blue and then to a bluish green when the above color reaction is applied.

The structural formula at the top of the next column is proposed for scillaren-A and its related degradation products. Acid hydrolysis yields the disaccharide called scillabiose, which is composed of rhamnose and glucose. The enzyme scillarinase can cleave the glucose residue selecively.

Rhamnose-Glucose Hellebrin Structure

scillaren
The cardiac action of the scillarens is essentially similar to that of digitalis, but this action is apparently less persistent than that of digitalis. The squill glycosides produce copious diuresis and are often active where digitalis and strophanthin fail to act, or act insufficiently, or where intolerance to digitalis exists. Because of its high therapeutic index and rapid elimination, it maintains compensation in those cases where prolonged treatment is necessary.

Scillaren-B N.N.R. is the amorphous component of the natural mixture of the glycosides occurring in squill, Urginea maritima. It is a fine, white or slightly yellowish white, odorless, granular powder, possessing a very bitter taste. It is freely soluble in water and in ethyl and methyl alcohols, 1 :S respectively. It is marketed as 0.5 mg. in 1 cc. ampules and is used the same as scillaren. Scillaren B is more water soluble and more active in the frog assay than scillaren A. The ratio of activity is about 3 to 5. Scillaren B is more stable than scillaren A, and the latter accounts for two thirds of the total quantity of the cardiac glycosides of squill.

Urginin N.N.R. is a mixture of two water insoluble glycosides, urginin-A and urginin-B, derived from squill, in the proportions in which they exist in the drug, i. e., about equal parts of each. It occurs as a pale yellow, granular powder possessing a slight characteristic odor and an extremely bitter taste. It is soluble in alcohol, and 1 cat unit is equal to 0.2 mg. per kilogram. It is marketed as 1.0 mg. tablets.

Hellebrin, found in Radix Hellebori nigri,3e is more active than ouabain when tested in the frog. It is related in structure to the squill glycosides and has been assigned the following tentative formula.