Active Ingredients. - Until quite lately, the chemistry of digitalis was a mass of confusion, owing to the want of concert between the different observers, and the careless use of particular names, which were employed in distinct and even in quite opposite senses. This confusion was at length substantially cleared up by the researches of Nativelle, the results of which are shortly summed up as follows in the treatise of the Husemans: Digitalis contains three peculiar substances, the active, crystalline, bitter-tasting digitaline;' the likewise active amorphous, bitter-tasting digitaleine; and an inert, crystalline, and tasteless substance. Of these three substances, digitaline is found only in the leaves, which also contain the other two bodies, while the seeds contain only digitaleine and the inert substance. The wild plant is, according to Nativelle, much richer in the active ingredients than the cultivated; the maximum richness is obtained in May, before the development of the flowers. The respective percentages of the above-named substances require further accurate researches for their determination. Nativelle found only 1/10 per cent. of crystallized digitaline in the leaves; of digitaleine, mixed, however, with the inert substance, he obtained 1 per cent. from the leaves and 2 per cent. from the seeds.

1 We here employ the nomenclature of Wiggers. Nativelle names the digitaline here referred to digitaleine, and, conversely, the digitaleine of our description he calls digitaline.

In the present article, the active crystalline body will be called digitaline, in accordance with the terminology which I have elsewhere adopted; and the active amorphous substance will be named digitaleine.

Digitaline forms small, white, silky needles, aggregated in masses, and having an exactly neutral reaction, an intense and lasting bitter taste - which, from the great insolubility of the crystals, only slowly develops itself - and no smell. Water - even boiling - ether, and benzol are almost powerless to dissolve it; but it is readily soluble in alcohol of 90 percent.; still more so in chloroform. Concentrated sulphuric acid dissolves it with a green color, which, on the application of bromine vapor, turns to red, but is restored to green on the addition of water. Nitric acid at first gives no color, but afterwards the solution becomes yellow. Muriatic acid turns it to a yellowish-green, which afterwards changes to emerald-green; water precipitates it from this solution as a resinoid mass. The chemical formula is not yet accurately established.

Digitaleine is a colorless, amorphous body; soluble in water in all proportions; and, like the first described substance, digitaline, is destitute of nitrogen.

The above is all that need be borne in mind by physicians in regard to the chemical and physical nature of the active ingredients of digitalis.

Concerning the commercial forms in which the active principles can be obtained, it will be sufficient to mention the so-called digitaline of Homolle and Quevenne, which is very insoluble in water, and evidently consists mainly of digitaline, as above described. This is the preparation best known in England, and perhaps the most to be relied on; but it would appear that there is no great difference between it and the preparations supplied by Merck, Marquart, and other German manufacturers of repute. They all contain both digitaline and digitaleine, besides other matters that are practically of no account, the first being very much the most active in its effects on the body, as has been proved by the experiments of Nativelle and of Schroff. Fothergill1 throws doubt on the superior activity of digitaline to digitalis itself, because of his finding a tincture of the leaves act more powerfully upon frogs. But this probably arose from the alcohol having dissolved little or nothing but the digitaline, while Homolle's preparation contained also digitaleine and digitalose. (There are four main substances which can be isolated in a pure state from the leaves, and which have poisonous or else physiological properties, viz., digitanin, digitalin, digitalein, and digitoxin (Binz). Commercial digitalin is a varying mixture of these, and the eclectic "digitalin" of still more uncertain composition.)

Physiological Action. - Taking the digitaline of Homolle and Quevenne as the standard, the following may be said to be the true physiological actions of digitalis, so far as authorities are agreed about them:

1 Prize Essay on Digitalis.

(1.) It is admitted on all hands that digitalis is a cardiac poison; given in large doses, it brings the heart to a standstill.

(2.) In doses which just fall short of a fatal effect, digitalis produces faintness, diarrhoea, nausea, and vomiting, with irregularity of the heart's action.

(3.) In still smaller doses, the heart's pulsations are much reduced in frequency, and the arterial blood-pressure is remarkably raised.

(4.) Doses large enough to slow the heart's action usually reduce the temperature.

Concerning the manner in which these effects are produced, there is, however, diversity of opinion. Traube put forward the theory that the action of digitalis on the heart takes place through the medium of the vagus; this is at first stimulated, and exercises increased inhibitory action on the heart, reducing the number of its beats; after a time, however (with large or repeated doses), there is vagus-exhaustion, the result of which is fluttering, rapid, and irregular cardiac action. It is evident, nevertheless, that the slowing action of digitalis is not exerted through the vagus-centre, since it is manifested in animals in which the trunks of the vagi have previously been divided; and on this ground, chiefly, certain authors have denied its action on the vagus altogether. Yet it can hardly be disputed that digitalis acts on the vagus, though only on its peripheral cardiac branches; for when atropine (which has the power to paralyze the vagus down to its very terminal twigs) has been previously administered to an animal, it is found that digitalis fails to slow the heart. Such is the argument of Traube, though disputed by various writers. The theory of direct stimulation of the cardiac ganglia giving rise to increased propulsive action of the heart, and overcoming the resistance of the inhibitory vagus branches, was put forward by Dybkowsky and' Pelikan, supported by Handheld Jones and Fuller, and acccepted by Fothergill; and the experiments of Eulenberg and Ehrenhaus, who plunged the separated, but still pulsating, hearts of frogs into a solution of digitaline, and observed strengthening of the contractions and reduction of the frequency of the beats, are considered by Ringer1 to prove that the "effect of digitalis is not due to any action on the pneumo-gastric nerve." One of the most recent writers on digitalis, Professor Ackermann, supports the theory of Traube; and, indeed, it is difficult to see how the evidence afforded by the control experiment of v. Bezold and Bloebaum with atropine can be set aside. Granting, however, that there is an action on the vagus, and that the primary excitement and subsequent exhaustion of the vagus-terminals account, in part, for the slowing and subsequent irregularity of the heart's action, there is no particular reason for denying the possibility of a simultaneous stimulation of the cardiac ganglia. There is, moreover, a considerable body of evidence tending to show that the muscular walls of the ventricles pass gradually into a tetanized condition, and are found so after death.2