* The solution employed by Briquet for this purpose contained 2 parts of iodine, 8 of iodide of potassium, and 250 of water. He found the action of the test to correspond closely with the observable effects of the medicine upon the nervous system. Thus, after the exhibition of 8 grains of sulphate of quinia in one dose, a precipitate sometimes appeared in half an hour, though more frequently at the end of two hours; after 4 grains, in two or three hours; after 2.5 grains, if any appeared, it was not till the expiration of five or six hours. The length of time, therefore, before the appearance of quinia is inversely proportionate to the quantity taken; and the same rule holds in relation to the period at which the effects are felt. (Trait. The-rap. du Quinquina, p. 220).

Another fact, noticed by the same experimenter, is that the quantity of the salt of quinia eliminated is directly proportionate to that introduced.

A third, also highly interesting, is that the elimination always ceases after a short time, generally little exceeding that during which the effects of the quinia persist. Thus, after a single dose of about 3 grains, the quinia disappeared from the urine in from 20 to 24 hours; after 30 grains taken during 12 hours, in about 40 hours; and after large doses taken for several days, in from60 to 80 hours. (Ibid., p 230).

* In reference to the effects of quinia on sight and hearing, I recently hud a patient who, under the full influence of the medicine, was affected with curious hallucinations, not only seeing either strange or familiar faces, but hearing unreal voices, sometimes from visible, sometimes invisible sources; and, as the patient was, on a moment's reflection, conscious that they were illusions, they were often sources of amusement. There was no fever, and no other evidence of cerebral excitement. The hallucinations vanished when sufficient lime had passed for the elimination of the medicine. (Note to the third edition).

Admitting quinia to be moderately stimulant, in small doses, to those cerebral functions which it specially affects, we have next to consider the question, whether the sedative effects undoubtedly produced by it, when largely given, are direct or indirect; that is, whether they proceed from an immediately depressing influence exerted by the quinia upon the encephalic centres, or are the consequences of a preceding state of excitation. To solve this question, it must first be determined, what are the immediate effects of a large dose of the medicine, sufficient to induce the ultimate prostration. Close observation upon the human subject and the lower animals has shown, I think, that so far as the brain is concerned, these effects are such as characterize excitation. The flushed face, the feeling of tension or fulness in the head, the sensitiveness to light, the buzzing and roaring in the ears, the vertiginous sensations, the involuntary muscular movements, the increased frequency of pulse and heat of skin, and the active delirium and convulsions which occasionally though rarely occur, are all proofs of stimulation and active congestion of the brain; and these proofs are still further strengthened by the fulness of the vessels of the pia mater, uniformly observed on post-mortem examination, and the evidences of positive meningitis which have been observed in a few instances. It is true that these phenomena of excitation are much less observable, when the same quantity is administered in small portions, at intervals of an hour or two; but, in this case, the stimulation from the several portions, not exceeding the degree of tonic action, is scarcely observable in the pulse, and subsides before being fully reinforced by the succeeding doses; while the secondary depression of the whole accumulates, and in the end becomes very obvious. The excitant effects of the large single dose may continue for two or three hours, when they gradually subside into a contrary condition, proportionate to the quantity taken, and, when this is in great excess, the prostration is in the end extreme. Now this is the ordinary and necessary result of over-stimulation; and it is altogether superogatory to imagine the existence of a directly depressing power in the medicine. The stimulation of an organ first excites its function; if it be continued and increased, the function is disturbed and becomes irregular; if still further increased, the organ is overwhelmed by the congestion induced, and its function is impaired or suppressed. The first excitement is thus followed by depression; and this is deepened through another physiological law, which determines that the excitability of a part is exhausted by over-exercise. Thus, after the first excitant effects of quinia above referred to have continued a short time, the cerebral centres become incapacitated for their duties through their congestion, and secondary exhaustion; and cease to send forth the influence necessary for the support of the functions over which they preside, or which they in any degree control. Hence the diminution or loss of hearing, the occasional loss of sight, the general feebleness of the muscular power, the trembling, the gradually diminishing frequency and force of the pulse, the coldness and pallor of the surface, and the universal prostration. Now this is a very different condition, in relation to therapeutic indications, from an apparently similar condition produced by a direct sedative to the nervous centres, or to the heart itself; and, though it might prove useful in certain cases if safely induced, yet, in determining upon the propriety of having recourse to it, reference must always be had to the possible clanger of the great over-excitement and congestion of the nervous centres involved. This point will again be brought under discussion, when we come to treat of certain therapeutic applications of quinia, proposed on the ground of its sedative properties.*

In explaining the effects of quinia on the system, a new path of investigation has been opened by Dr. H. Bence Jones, through the discovery in the animal tissues of a substance strongly resembling quinia in its reagencies; not only exhibiting the same remarkable fluorescence in solution, but responding in like manner to various other tests of quinia. But much further investigation is requisite in order to form a satisfactory opinion of the relation of this new substance with quinia, and how far any supposed similarity or identity between them can have a bearing on the systemic influence of the cinchona alkaloid.

* Some experiments of Briquet upon dogs would seem to prove a direct sedative influence of quinia upon the motor power of the heart. By injecting quantities of sulphate of quinia in solution, varying from 7.5 to 80 grains, into the external jugular vein of dogs, he found the force of the heart's contractions, as measured by the haemadynameter of Poiseuille, to be diminished in proportion to the quantity used, very slightly by the first quantity, and very greatly by the lust, which caused the speedy death of the animal by syncope. In other experiments, in which similar solutions were made to enter directly the cerebral vessels, the brain was excited, and the force of the heart's pulsation considerably increased. (Traite Therap. du Quinquina.) The inference from these results is that quinia is directly stimulant to the brain, and, through it, is capable of exciting the heart; while, introduced into the heart itself, it has a tendency to paralyze that organ. A great objection to these experiments, so far as the heart is concerned, is that, in order to produce the least depressing effect on that organ, the quantity of sulphate of quinia, introduced into the jugular vein, must produce a much stronger impregnation of the blood reaching the heart, than can be produced by any amount of the medicine swallowed, which is eliminated by the kidneys almost as fast as it is absorbed. The inference is, that no direct observable depression of the heart would follow the internal administration of quinia. But, even though we should admit the entire accuracy and relevancy of these experiments, they do not invalidate the force of the argument in the text, in relation to the use of quinia as a sedative. Whether the depression in the actions of the heart, produced by large doses, depends wholly upon the secondary depression of the brain, as supposed in the text, or partly upon that, and partly upon the direct action of the quinia on the heart, in either case the danger of an over-excitement of the brain, which the same experiments show to result from the medicine, must be encountered, whenever the sedative effect on the circulation is resorted to as a therapeutic agency.