In small doses quinine exerts a distinct stimulant effect on the cerebrum, increases the mental activity, and even exhilarates in some mobile constitutions. As some hyperaemia is caused by it, the resulting cerebral stimulation is probably secondary to this change in the vascular condition. In full medicinal doses, as the quinine accumulates in the brain, a sense of fullness in the head, constriction of the forehead, tinnitus aurium, more or less giddiness, even decided vertigo, may be produced. Dullness of hearing results from considerable doses, and deafness has in rare cases been permanent. In a long experience of its use and extended observation, no case has come under my notice of permanently impaired hearing, although the temporary condition is usual. According to Knapp, Moos, and others, amaurosis is produced by very large doses. White atrophy of the optic disks occurs, and most of the vessels disappear from the field. This must be due to strong contraction of the vessels, since this condition is quite curable, the ordinary appearance of the retina being restored in most of the cases. Permanent atrophy of the optic nerve is, however, an occasional result. Amblyopia is frequently produced by the use of considerable doses kept up for some time. It is recovered from readily by suspending the administration of the remedy and taking the necessary steps to improve the intraocular circulation. In actually toxic doses all of the above symptoms have been intensified. There are intense headache with constriction of the forehead, dimness of vision or complete blindness, deafness, delirium or coma, dilated pupils, weak, fluttering pulse, irregular and shallow respiration, convulsions, and finally collapse and death. It is excessively rare to encounter such severe cerebral symptoms.

The influence of quinine over the functions of the spinal cord is yet sub judice. Chaperon some time ago demonstrated that quinine lessened and ultimately abolished the reflex function of the spinal cord. This result he decided was due not to immediate action on the spinal cord, but to stimulation of Setschenow's center of inhibition of reflex movements. Brunton, who has repeated Chaperon's experiments, has found them to be correct. The observation of Schlockow, that the first effect of quinine is to increase the sensibility of the reflex function of the spinal cord, has much probability in its favor. Heubach has also, after moderate doses, observed some evidences of the existence of reflex irritability, but the experiments of Brunton show that these reflex effects decline with the increasing stimulation of the inhibiting center. Brunton's experiments were also directed to ascertain whether the sulphuric acid in combination with the quinine was responsible for the effects observed, but the result proved that quinine is the active agent in stimulating Setschenow's inhibiting center.

As quinine depresses the functions of the sympathetic system, its action is opposed to that of agents which have the power to promote uterine contractions, hence, a priori, it would not seem to be aborti-facient. Very numerous and conflicting statements have been put forth, because there are no exact data. The few cases in which uterine action followed the administration of quinine were, doubtless, due to malarial intoxication or to other causes, and hence the association of uterine action with the effects of quinine was accidental. The innumerable instances in which quinine has been given during the existence of pregnancy, without initiating contractions of the womb, are certainly conclusive against the view of its abortifacient power. While it is not a special uterine stimulant, it may exert such an action indirectly. When uterine inertia is due to depression of the vital . forces, quinine, in moderate doses, then becomes a valuable stimulant, and is utilized for this purpose in obstetric practice.

The diffusibility of quinine and its rate and mode of elimination have been studied by Bence Jones, Ciotti and Albertoni, and Kerner. Jones in his researches availed himself of the fluorescent property of animal tissues, possessed also in a high degree by the alkaloids of cinchona, especially quinine. To this substance, as it appears in animal tissues, Jones gave the name "animal chinoidin," but he was not aware that fluorescence is a property possessed by large numbers of animal and vegetable bodies. Nevertheless, he recognized the fact that the diffusibility of quinine could be estimated by the increase in the fluorescence of animal textures, and he thus ascertained that in a half-hour after the administration of quinine a positive gain in fluorescence of the crystalline lens is observed. It is probable that under some circumstances—a catarrhal state of the mucous membrane, for example—a portion of the quinine taken fails to be absorbed, and is consequently excreted by the intestines (Byasson). The effect of this agent on the secondary assimilation is involved in more or less doubt. Opposing opinions have arisen from the different points of view taken. In the normal condition quinine, in small quantity, stimulates the nutrition, and increases the excretion of waste products—urea, uric acid, creatinin, extractives, etc.; but, in considerable doses, the opposite condition obtains—the decrease in the quantity of uric acid is especially well marked (Ranké,Kerner)—and when administered in malarial fevers all the products of waste are greatly increased. The conditions attending the use of the remedy, therefore, influence the result. Considerable doses in the normal state diminish the excretion of urea, uric acid, creatinin, and phosphoric and sulphuric acids (Kerner). Strassburg, however, failed to find any change in the carbonic acid. According to the observations of Cutler and Bradford, quinine has an obvious effect on the globular richness of the blood, increasing the relative proportion of the white, and diminishing the red globules. The action of quinine on the spleen is still sub judice. Piorry was the first to note a reduction in the size of the organ produced by quinine, but he had an exaggerated notion of the nicety by which a difference in the size of an organ could be made out by the ples-simeter and hammer. Küchenmeister examined the subject experimentally in 1851, with negative results, but afterward, operating with larger doses, obtained confirmation of Piorry's view. Mosler, after dividing all the nerves of the spleen, ascertained that quinine in large doses still acted on the contractile elements, and reduced the size of the organ. Jerusalimsky, in an elaborate research, has established the same fact. That the enlarged spleen of malarial infection is reduced by quinine is an undoubted clinical fact. From these positive observations it must be concluded that quinine does act on the spleen, notwithstanding there are numerous negative statements. It follows, hence, that the diminution in the red and increase of the white corpuscles may be due to this action.

Quinine diffuses out of the blood into the urine, chiefly, but also into the sweat, saliva, milk, and pathological exudations (Kerner, Briquet, Binz). jürgensen found quinine in the urine in ten minutes after the hypodermatic injection. Thau had evidence of its presence in the urine in a half-hour after the ingestion of a half-drachm dose each by two persons, and he holds that the maximum elimination takes place in about eight hours, but the excretion is not completed until two days after the administration. According to De Renzi, quinine remains in the organism a variable number of days, and may indeed be discovered in the urine on the third day; in a special case, as late as seven days. Binz also finds that the elimination of quinine is variable and rather slow, the maximum being excreted within forty-eight hours. From the time the agent appears in the urine, the systemic action is manifest, and the maximum effect of any given dose must be experienced in advance of the period of maximum elimination, which Thau places at eight hours. According to Kerner, quinine appears in the urine in a somewhat modified form.

The action of quinine has occasionally been attended by the appearance of an eruption on the skin. Sometimes the exanthem has been in the form of an erythema, sometimes it has assumed the appearance of urticaria; again, it has seemed to be herpetic. There is, in fact, no constant and invariable eruption, and many of the reported cases are open to the suspicion that the appearances on the skin are merely accidental, and not causative.