Active Ingredients. - These consist of a volatile oil, and a peculiar, crystalline, neutral principle calledsantonine, C15H18O3, which, though procurable from other plants, is contained in quantity worth extracting only in the present one. It occurs in flat, four-sided, colorless prisms, which are inodorous and feebly bitter; in cold water it is scarcely soluble, requiring 10,000 parts, and in boiling water very little more so, requiring 5,000 parts: it is soluble in solutions of lime and alkalies, abundantly so in chloroform, and in boiling rectified spirit, but not at all in dilute mineral acids, though strong nitric acid is said to convert it into succinic acid. Santonine is fusible, and sublimes at a moderate temperature; the crystals, on continued exposure to light, become disintegrated, and assume a yellow tint.

Physiological Action. - Few medicinal substances have more curious or interesting physiological effects than santonine. Apart from its fatal action on intestinal worms, especially the round worm (Ascaris lurnbricoides), to which it is the deadliest of all anthelmintics, it has remarkable influences on the animal organism generally. The most singular of these, though not the most important, are the color-changes. The urine has long been known to become deep orange-yellow during its use, and to Mr. Spencer Wells is due the observation (1848) that vision also becomes affected in such a manner that objects look as if they were seen through a yellow medium.1 Since that time the phenomenon of colored vision has been closely studied by many investigators, but it is not definitely cleared up. The most complete researches are those of E. Rose.2 This observer distinguishes two forms or grades of the colored vision; the first, or earliest, is a violet coloration which is by no means a constant phenomenon, but, when seen at all, is more intense than the yellow tint which follows, and is perceived most strongly in looking at dark objects, while the yellow tint, on the contrary, is best seen against white or fully lighted surfaces. All these phenomena of colored vision are of brief duration, much briefer, for example, than that of the coloring of the urine. Besides the peculiar appearance of surrounding objects, there is one very remarkable visual effect, which Rose declares to be constant; the spectrum, when looked at by the patient, is apparently shortened, especially at the violet end. It is extremely difficult to conjecture what the mechanism of these symptoms can be. The only change in the eyes observable from without is that the pupils are always dilated3 (the dilatation is so considerable as to cause amblyopia); there is no staining of the conjunctivae as with any diffused coloring-matter; and it may be noted here, by the way, that it is not possible to produce the colored vision by the local application of santonine to the eye. Neither the fluids nor the solids of the eye are at all colored by the action of santonine; there is no jaundice or other coloration of the skin; and although the urine, as already mentioned, is dark colored, the change does not depend on bile-pigment, but on some pigment formed probably in the kidneys. The latter conclusion is based on the fact that the coloring-matter is not to be found in the blood-serum, which is quite unchanged, nor in the lungs, the retina, the sweat, or in the amniotic water of pregnant animals. Rose himself considers that the yellow appearance depends on the retina becoming hy-perasmic, and the violet appearance on a positive injury to the fibres of the optic nerves, independent of any central lesion. The phenomena are clearly different from those of the hallucinations of sight which occur in migraine and some other nervous affections, inasmuch as they are never observable when the eyelids are closed. There is much difference between the reports of different observers as to the possibility of a long lasting amaurosis or other serious damage to vision.

1 Mr. Wells's observation was independent; the coloration had, however, been noticed as an occasional effect of worm-seed by Hufeland as early as 1806, as an occasional effect of santonine by Callord (1843), and as a constant effect of santonine by Itzstein (1846).

2 Virchow's Arch., 1868, p. 233.

3 Even this is disputed, but I personally believe it is a constant symptom.

Symptoms of general severe poisoning with santonine, though very rare, have occurred from time to time. There have been several cases of poisoning by santonine lozenges, and two or three from taking excessive doses of worm-seed. The quantities of santonine that have proved poisonous in this accidental manner seem to have ranged from 1 1/2 up to 10 grains for children. Among these cases there is one in which a child of 5 1/2 years was actually killed in fourteen hours by two doses of about a grain each. Upon this last there rests, however, some degree of doubt, since far larger doses have often been taken almost or quite without bad effect. The symptoms of santonine-poisoning are partly concerned with the alimentary canal, and partly with the nervous system. The disturbance of the former is indicated by vomiting or retching, pain in the abdomen, anxiety, and restlessness; of the latter by twitchings of the muscles of the face and of the limbs, and by obscure epileptiform or tetaniform symptoms. The pulse seems to show a diminution both in heart-force and in arterial tone. The general phenomena disappear in twelve or fourteen hours if recovery takes place at all; but the coloration of the urine persists for some time longer.

Animals which have been poisoned by santonine exhibit marked hyperaemic changes in the cord and medulla oblongata, in the membranes of the brain, and in the lungs; the appearances in the nerve-centres are more considerable in dogs than in rabbits. The more powerful physiological effects of santonine are best produced by injecting a chloroformic solution beneath the skin; for when taken by the mouth the crystalline santonine in part passes through the alimentary canal unchanged; the remainder is taken up as an alkaline salt into the blood. (Santonate of soda, by the way, is an available form in which to give santonine for the physiological effects; many of the experiments of Rose and others were made in this manner.) As regards the ultimate chemical destiny of santonine in the body, it is not possible at present to speak with certainty; the coloring-matter which appears in the urine has not yet been completely identified in its chemical relations.

Therapeutic Action. - Though it will not improbably be employed, at some future time, for other medicinal purposes, santonine is at present practically known only as an anthelmintic. It is tasteless and inodorous, and can thus be given with great convenience. To the round-worm it is absolutely fatal, and in somewhat less degree to the smaller ascarides. Its effects are most evident in cases where the presence of worms has given rise to intermittent or remittent febrile symptoms - the so-called "worm-fever." It should be given, like most other anthelmintics, on an empty stomach, and preferably at night and in the morning.

Preparations and Dose. - Santoninum: for adults, gr. ij. - vi. (.13 - .40); Trochisci Santonini (adults) No. v - x.