Active Ingredients. - The question which of the constituents of hellebore root are active, has attracted renewed interest of late years on account of the discovery of the glucoside Helleborin, by Bastick (1853), the confirmation of this by Marme and Husemann, and the discovery by the latter observer (1864) of a second glucoside, Helleborein. The former of these is not found so largely in the Helleborus niger as in certain allied species. It is crystalline, in concentrically grouped shining white needles, odorless, and of neutral reaction; in the solid state it is tasteless, but the alcoholic solution is very acrid and burning to the mouth. It is insoluble in cold water, little soluble in ether and in fats, readily soluble in rectified spirits and in chloroform. Formula C30H42O6. Helleborein (C26H44O16) crystallizes out of a very concentrated alcoholic solution in collections of fine, nearly colorless transparent needles, which quickly turn chalk-white under the influence of the atmosphere. The evaporation of a watery solution leaves a grayish-yellow resinous powder, which has no distinct smell, but is strongly provocative of sneezing. Helleborein is very soluble in water, little so in alcohol, not at all in ether. Since the discovery of these two substances (which will be again considered under the heading of Physiological Action), it is doubtful whether the older conjectures, that the action of hellebore depends upon an acrid oil and a "volatile acid," can have been just. The active volatile ingredient may be helleborein, which is faintly or not at all acid in reaction, and is not affected by boiling in the alkalies or baryta; but its volatility is limited.

Physiological Action. - The Helleborus niger emits no particular odor until bruised. The fibres of the root, which are the part employed in medicine, have a disagreeable smell; their taste while fresh is penetrating, and, though neither bitter nor very warm, it leaves a long persisting impression upon the tongue. Grew, in his work upon Tastes, describes its effects as benumbing and as inducing a paralytic stupor - comparable to that produced by drinking or eating anything too hot. When the fibres have become dry, their acridity is much diminished, but the nauseousness and the bitterness are more marked.

Whichever may be the constituents that determine the energy of hellebore, there is no doubt of its being a violently acrid poison, for even the flowers when crushed and applied to the skin produce redness and vesication. This is remarkable, since in these external effects the root and the leaves do not participate. The effects produced by swallowing an overdose are vomiting, colic, purging, great thirst, sense of suffocation in the throat, and of burning in the oesophagus and the stomach: these are accompanied by a painful pricking and swelling in the tongue and fauces, and the secretion in the mouth of a considerable quantity of viscid mucus; and are eventually followed by convulsions, cold sweats, a feeble pulse, and death. Post-mortem examinations show, that when death is caused by hellebore the stomach and intestines are much inflamed, and that the rectum more particularly becomes affected; thus indicating a certain analogy between the action of hellebore and that of colchicum.

It is interesting to append to this description of the physiological action of hellebore, as such, the observations that have been made on the effects of the two glucosides. Helleborin is found to be a very energetic substance. Marme found that 1 1/4 grain, administered subcutaneously, killed frogs; half the quantity, by the stomach, killed pigeons; 3/4 grain to 1 1/2 grain killed rabbits; less than 4 grains were fatal to dogs. It had no effect upon entozoa. It was found to exercise no action upon the skin, and to exert a less intense action on mucous membranes than helleborein. Helleborein, administered by the stomach to mammalia, caused licking and chewing movements; teeth-grinding; a certain amount of salivation in cats and dogs; vomiting in dogs and birds; pains in the belly (apparently) in dogs and rabbits; efforts at evacuation in dogs. On dissection the mouth and oesophagus were healthy; in pigeons the crop was always extensively inflamed; in mammalia the stomach and intestines showed signs of irritation in varying degrees, from simple increase of secretion to inflammation of high grade with extravasation of blood. The remoter actions of the drug fell upon the nerve-centres, especially the brain, paralysis of which appeared to be the cause of death. In animals, a period of excitement and restlessness was followed by paresis of the hind limbs, with tremor and vacillation of the whole body; a further stage was marked by profound paralysis and anaesthesia: cats alone recovered comparatively soon from this state. Marme and Husemann always detected marked congestion of the membranes of the brain and cord: in rabbits there was also diminished consistence of the cord, and extravasation of blood into the cranial cavity. Functions of other organs were affected in much the same way as by narcotic agents in general. Urinary secretion somewhat increased (in cats only); respiration slowed during narcosis; hypostasis and hyperaeemia appeared in the lungs after death; the heart's action was not reduced except by the heaviest doses; especially in frogs and dogs the cessation of pulsation was very late. The pupils widely dilated in narcosis, but contracted post-mortem, under electric stimulus.

The experiments of Marme with helleborein show interesting differences of effect from the above. The action is both local and remote; locally it does not affect the skin, but it is intensely irritative to the mucous membrane. Absorbed, it exerts a powerful influence on the heart and the intestinal canal; yet it does not seem so deadly to animals, in equal dose, as helleborin; perhaps because only a part is absorbed unchanged, the remainder being split up into products which are inactive (e. g., helleboretin) when taken into the blood. Very small doses administered by the stomach for a long period produce a cumulative effect, shown by loss of appetite, nausea, and vomiting, which disappear rapidly on suspending the drug; and occasionally this mode of administration has produced (as larger doses will) pain, increased secretion, and gastro-enteritis. These effects, however, are perhaps not so liable to result from helleborein obtained from the black hellebore as from that of other species, especially the H. viridis. The special action of helleborein on the heart resembles that of digitalis, but is quantitatively much weaker: small repeated doses slow the heart; larger doses hurry its action, and then usually arrest it suddenly; the action is through the vagus, and blood-pressure is heightened both in the slowing and in the hurrying grade. Respiration lasts longer than the heart's action; respiration is nevertheless affected. The glands (especially the salivary and the kidneys) are affected, and the uterus. Respiration is at first quickened, then made slow and difficult. Salivation is always produced, whatever way the drug is introduced into the system; diuresis is constant, and the kidneys are hyperaemic after death; in female animals the uterine mucous membrane is invariably congested. There is semi-paralytic weakness of the limbs, and (after very large doses) there are severe convulsions.

Therapeutic Action. - Previously to the introduction of medicines derived from the mineral kingdom, the value attached to hellebore was immense. The early physicians commended it in the treatment of insanity, both maniacal and melancholic, and there is no doubt that great benefit has followed its employment in the last named. It has also been given with apparent success in dropsy, worms, and cutaneous disorders.

and as an emmenagogue; but this last-named use may be reasonably supposed to depend upon the great cathartic powers inherent in hellebore.

Stille says that hellebore in small doses appears to stimulate the abdominal organs, augmenting the secretion of the liver and of the pancreas, quickening the peristaltic movements of the bowels, and increasing the catamenial discharge. Haemorrhoidal discharges are likewise increased by its use.

I have often prescribed the tincture of hellebore in doses of from five to fifteen drops every two or three hours, in cold water, with complete success in dropsical effusions, and particularly in general anasarca following scarlet fever uncomplicated by organic disease.

From what has been above mentioned as to the physiological action of the glucosides helleborin and helleborein, it is possible that we may hereafter derive new and valuable therapeutic benefits from these substances. Helleborein, in particular, seems marked out, as Marme observes,1 for employment in heart complaints and dropsy; its solubility in water, and the impunity with which it can be subcutaneously injected, give it important advantages.

Preparations and Dose. - Tinctura Hellebori, m,v.-3ss. (.30 -2.); Extractum Hellebori, gr. j.-v. (.06 - .30).