An inquiry into the physiological and medicinal properties of the veratrum viride : together with some physiological and chemical observations upon the alkaloid veratria obtained from this and other species : being the prize essay to which the American Medical Association awarded the gold medal for MDCCCLXIII

Front matter

“VERATRUM VIRIDE.

a

AN INQUIRY

Section Second. Chemistry And Pharmacy Of Veratrum Viride

Division First.—Chemical History 7 %

Division Seconp.—Process for Obtaining the frat rnecaiee an Alkaloid of Veratrum Viride . ‘: . i :

Division Tarrp.—Chemical Tests and Rengearia for the disaiaitcas of the ved loid, and its Comparison with Alkaloids obtained from other Species of Veratrum. . . é

Division Fourta.—Dose and Mode of Admnbatotinidien “ : °

- SECTION THIRD.

PHYSIOLOGICAL ACTION ON ANIMALS.

Division First.—Experiments elucidating the Physiological Action of Veratrum Viride on Animals . 3 ; E

Division Szconp.—Experiments elucidating the Physiological deta of ihe Resinoid Principle of Veratrum Viride on Animals

Division Tairp.—Experiments elucidating the Physiological Action of the Alkaloid Veratria obtained from Veratrum Viride and from other Species on Animals . ; ;

Division Fourta.—Experiments elacttdlting the Physiological pe of Veratum Viride on Frogs and Bats, by the Examination of the Circulating Blood with the Microscope : . . .

Section Fourth. Therapeutic Applications

Division First.—Therapeutic Application of Veratrum Viride, with the relation of a few Cases in point ‘ : . : = ° . .

Page

13 17

6 CONTENTS.

Division Srconp.—Therapeutic Application of Veratrum Viride in Typhus and Typhoid Fevers. . 5 : : J 5 “ ;

In Phthisis, also, as a Means of Diagnosis in Diseases of the teak and Heart Division Tutrp.—Therapeutic Application of the Resinoid of Veratrum

Viride : . 5 * Division Fourra.—General Hencpelk of the Alkaloid Votatria, inn Varina Viride . ° S 5 ; ° “ °

SECTION FIFTH. Page

53 55

SUMMARY OF THE PHYSIOLOGICAL AND THERAPEUTIC ACTION OF VERATRUM

VIRIDE ON MAN.

Division Frrst.—General Action . ‘ A 4 . . : . * Division Seconp.—Its Action on the Vascular System . 5

Division Totrp.—Its Action on the Respiratory System. A : . ° Division Fourru.—Its Action on the Nervous System . ‘ ° . ° Division Firra.—Its Action on the Muscular System . s ° . ° Division Srxru.—Its Action on the Secerning System . ; ; . ; Division SeventH.—Its Action on the Alimentary Canal ; . 5 Division Eicuta.—Emetic Action. . . ° . ; . . .

Division Ninta.—Recapitulation— First Degree of Operation . : ° a . Shere Second Degree of Operation ; 5 ; : 4 5 Third Degree of Operation . : 2 : . ; : . . Fourth Degree of Operation ; s 4 ° . ° . .

Division TentH.—Veratrum Viride in large and poisonous doses . ° ° Division ELeventH.—Cumulative Action . ° ° . ° .

SECTION SIXTH. Modus Operandi . . ° : : ° °

61 64 66 67 68 68 70 70

72 73 73 73 75 77

PRIZAEH.ESSA Y.

PHYSIOLOGICAL AND MEDICINAL PROPERTIES OF THE VERATRUM VIRIDE.

Section First. Botany And Physical Characteristics Of Veratrum Viride

Nat. Orp.—Melanthecezx.

Common Names.—American hellebore. Swamp hellebore. Indian poke. Itch weed, &c. §C.

Part used in Medicine—T he root.

THE Veratrum Viride has a perennial, thick, fleshy root, “the upper portion of which is truncated, the lower solid, and beset with numerous whitish fibres or radicals.” “The stem is annual, round, solid, striated, pubescent, and from three to six feet high; being throughout the greater part of its length closely invested with the sheathing bases of the leaves.

“The leaves are alternate, and gradually increase in size as they descend ; the lower ones are from six to twelve inches long, oval, - acuminate, pubescent, strongly ribbed, and plaited, the lower part of their edges meeting round the stem. The upper leaves are gradually narrower, the uppermost and the bracts, linear-lanceolate.

“The flowers are numerous, yellowish-green, and arranged in compound racemes, axillary from the upper leaves, and terminal. Each flower is accompanied by a boat-shaped acuminate, downy bract, much longer than its pedicle. Peduncles roundish, downy. The perianth is divided into six oval, acute, nerved segments, of which the alternate ones are the longest, and all contracted at the base into a sort of claw, with a thickened cartilaginous edge. The stamens are six, with recurved filaments and roundish. Anthers two-lobed. Ovaries three, cohering with acute recurved styles as long as the stamens.

“The fruit consists of three capsules united together, and separating at top, and dehiscing on the inner side.

It is indigenous in almost every part of the United States, growing in wet meadows and upon the banks of rivers.

“Tn this connection it may perhaps be asked, What are the botanical differences between Veratrum viride and Veratrum album?

“To this inquiry, I must answer, that all which I have ever been able to discover consists in the fact that the edges of the segments of the perigone, in Veratrum viride, are slightly incrassated, and contracted below their middle, which is not the fact in Veratrum album ; and that the general aspect of Veratrum viride is coarser and rougher, and it is of a darker green color. These are small characters, but they appear to be permanent, incapable of change by climate, soil, culture, &e. &c.”!

The root is the part used in medicine, and it should be gathered in the autumn after the top has died. It might probably be equally active in its medicinal effects if gathered very early in the spring, but this can seldom be done, for it commences to grow before the snow and frost have fairly disappeared.

When freshly gathered the root has a strong, pungent, acrimonious taste, and when bitten, leaves a prickling and bitter taste in the mouth; but it loses most of this acrimonious effect by drying. In order to preserve the root properly, it should be cut in fragments, well dried at a low temperature, and kept in a dry place, for if kept where it is damp it deteriorates very quickly.

The leaves possess but little of the active properties of the root.

History.—It was known and used by the Indian before the occupation of this country by the European. The best description of its early history, since that time, is given in Bigelow’s American Medical Botany, though neither Bigelow nor Ware understood its therapeutic powers in acute diseases, but, like the ancient Ascleepiade, with their preparations of “ white hellebore,” used it only in chronic affections.

'Tully’s Materia Medica, vol. i. p. 215.

About the year 1830, Drs. Tully and Ives, of New Haven, investigated very fully the therapeutic properties of the plant.

The attention of the medical profession was particularly called to its use in the treatment of acute diseases, by Dr. Charles Osgood, _ of Providence, R. I., in an essay written for the American Journal of Medical Sciences, 1835.

Dr. Osgood, in a very modest manner, gives his preceptor, Professor William Tully, the credit of first calling his attention to its proper therapeutic powers, but Dr. Osgood, like modest men in general, underrates his own merits, and has written a very truthful and praiseworthy essay, which has been studied by all who have followed in his footsteps, but has been excelled by none; it still stands unrivalled, the best monograph that has been written on the plant.

The writer of this “ Inquiry ” first learned the knowledge of the physiological and therapeutic properties of the plant from Dr. Osgood, in 1849, and he has constantly used it since that time.

By the majority of the profession, but little attention was paid to Dr. Osgood’s essay, until the use of the plant was revived by Dr. Wm. C. Norwood, of Cokesbury, South Carolina.

Dr. Norwood published a pamphlet on the therapeutic properties of Veratrum viride in 1851, and disseminated it very widely; it has gone through three editions.

After this time the properties of the drug were discussed in many of the medical societies of this country, and many excellent articles have appeared from time to time, in the medical journals, especially in those of the South and West.

In 1856, the Section of Materia Medica of the New York Academy of Medicine, appointed the author of this work to prepare a monograph upon the plant, and open a discussion upon its properties in the Academy.

In the same year the Harveian Circle, of the city of New York, appointed Drs. Percy, Miller, and Belden to perform a similar duty for that Society.

In 1858, the Massachusetts Medical Society appointed Drs. Cutter, Richard, and Ingalls, a committee to bring this remedial agent to the direct attention of the Society, a task which they performed in May, 1858, and again in 1861. In the meantime many able papers appeared upon the uses of the plant, in the medical journals, among the best of which may be mentioned those of Professor M’Gugin, of the lowa University.

Section Second. Chemistry And Pharmacy Of Veratrum Viride

DIVISION FIRST.

CHEMICAL HISTORY.

Dr. CHARLES Oscoop, of Providence, R.I., published the results of some chemical experiments upon this plant in the American Journal of Pharmacy, vol. i., second series. He obtained a white, inodorous, and very acrid powder, which he thought to be the alkaloid principle of the plant, but no satisfactory experiments were made by him on the point.

In the 9th volume of the same journal, Thos. A. Mitchell gives & proximate analysis of the plant, and states that he obtained an active principle, in the form of a white powder, but he was unable to make any chemical examinations, as the amount obtained was very small.

In the 10th volume of the same journal, Henry W. Worthington gives a more complete analysis of the plant, and states that he obtained “an alkaloid substance identical with veratria,” that it “was soluble in dilute acids,” and that “the sulphate, tartrate, and oxalate were crystallizable salts.”

To Mr. Worthington, then, is due the honor of having first announced by publication, and demonstrated by chemical tests that an alkaloid existed in the plant.

In the same journal for May, 1857, Mr. Joseph G. Richardson gives an elaborate chemical essay on this plant. After reviewing what was already known and giving the results of various experiments for obtaining the alkaloids, Mr. Richardson gives several tests for its detection, and also proves by many separate analyses that the alkaloid obtained by him was identical in its chemical reactions with the alkaloid obtained from Veratrum album.

In 1857 the author of this monograph presented for the inspection of the Fellows of the N. Y. Academy of Medicine, 38 grains of the pure alkaloid obtained from Veratrum viride, and described the process by which it was obtained; this was in a very fine, white, amorphous powder, possessing all the physical properties of veratria. The Academy did not publish this analysis.

In 1862 Geo. J. Scattergood made an elaborate investigation of the alkaloid obtained from both species, the results of which he presented in an essay to the American Pharmaceutical Association, at their meeting, August, 1862, and it may be found entire in their printed proceedings of that year.

DIVISION SECOND.

PROCESS FOR OBTAINING THE TINCTURE, RESINOID, AND ALKALOID.

Tincture-—The root, coarsely powdered, is treated with alcohol fortius, sp. gr. 0.817, by percolation, the alcohol distilled off, and the residuum evaporated to an extract over a water bath until it is nearly dry, or until it ceases to become lighter upon being weighed at intervals of an hour or two.

To make the concentrated tincture spoken of in this work, one part of this extract is dissolved in ten parts of alcohol, 0.817, and filtrated.

Resinoid— Veratrum viride root coarsely powdered is treated with alcohol, 0.817, by percolation, the alcohol distilled off, and the residuum evaporated to a soft extract. A saturated solution of this extract is made in alcohol, 0.817, and filtered slowly into a large quantity of cold water previously acidulated with sulphuric acid, and kept constantly stirred. The fluid is filtered off, leaving most of the resinoid substance in the beaker; fresh acidulated water is added, well stirred, and the whole then thrown on the filter, and repeatedly washed with cold water, until every trace of sulphuric acid is removed; it is then dried. This substance I have called resinoid. By repeated examinations, it is entirely free from every trace of alkaloid.

It is also free from the extractive substances that are soluble in water.

I have used this in the form of tincture, made by dissolving it in alcohol 0.817, of the strength of 51, grain of the resinoid to each minim. This resin is of asoft consistence; about 25 per cent. of it is soluble in ether, and the remainder is harder and more friable.

Both resins produce the therapeutic action above noted, but the alcoholic resin is more uniform and certain in its action than the ethereal. The éther extracts the oily portions.

Alkaloid.—The processes adopted by Worthington, Richardson, and Scattergood may be found in the works already referred to.

The process that I have adopted for obtaining the alkaloid has differed from that recommended by either of these gentlemen.

Any quantity of the coarsely-powdered root of the Veratrum viride is moistened with water and packed into a percolator; water acidulated with hydrochloric acid is added, sufficient to cover the root, and allowed to stand for twenty-four hours,

It is then allowed to percolate, and the first portion of the fluid which contains most of the strength of the root, is kept by itself; fresh acidulated water is added, until the root is exhausted.

The latter liquid is evaporated to about one-quarter its former bulk, filtered, and the first portion of the percolate mixed with it; soda is then added so long as a precipitate forms.

The precipitate is washed in a small quantity of cold water and dried; it is then treated with ether, the ether is filtrated off, and allowed to evaporate.

This mass is then treated with water acidulated with hydrochloric acid, filtered, and ammonia added so long as a precipitate forms; the fluid is filtered off, the precipitate washed in a small quantity of cold water, and mixed with a small amount of animal charcoal, which has been previously moistened with a little alcohol.

The whole is put into a flask and alcohol added to it; the flask is put in hot water, and the hot alcoholic solution filtered off, and more alcohol added, which is treated in the same way.

The whole of the alcoholic solution is either distilled or evaporated, according to the quantity of alcohol used; and the soft mass that is left is treated with successive stamina of boiling be acidulated with hydrochloric acid.

This solution is filtered and the alkaloid is precipitated with ammonia.

The precipitate when dry is treated with ether, filtered, and the ether allowed to evaporate slowly.

The alkaloid is in a semi-crystalline state and of a slightly yellow tinge.

To prevent the excessive and painful sneezing caused by inhaling this alkaloid, I have found it advisable, when manipulating with it, to anoint the nostrils as far up as possible with castor oil, and to tie over the nostrils a piece of moistened sponge.

DIVISION THIRD.

CHEMICAL TESTS AND REAGENTS FOR THE DETECTION OF THE ALKALOID.

As I have obtained veratria from Veratrum viride, it is, if precipitated, a pure, white, amorphous powder; if from the evaporation of ether, it is semi-crystalline and of a slightly yellow tinge.

It is of an acrid and burning taste, but is not very bitter. It is necessary to be exceedingly cautious in handling it, for if a very minute portion is breathed up the nostrils, it excites violent sneezing, which is difficult to check, and occasionally produces alarming symptoms.

Its formula is probably the same as that of commercial veratria, C,,H,.N 0,Ve.

If a small quantity of veratria be placed upon platina and held over a flame, it fuses at a gentle heat; if it be now removed it solidifies as it cools, and becomes a semi-transparent yellow mass; but, if the heat be continued, it swells up and is gradually dissipated. It is insoluble in water, but readily soluble in ether, alcohol, chloroform, and benzole.

It neutralizes acids, and forms salts which are soluble in water; they are of an acrid and persistently burning taste, and produce a considerable degree of irritation if rubbed upon the skin.

In the experiments I give below I have as closely as possible followed the experiments performed by my friend, Professor T. G. Wormley, upon the purified veratria (of Murk’s manufacture) from Veratrum sabadilla, and published by him in the Ohio Medical and Surgical Journal, July, 1860.

My object was to institute a more elaborate research than that previously made by Mr. Richardson, and ascertain if the alkaloids from the different plants were identical in their chemical reactions.

For the purpose of experimenting, a given quantity of the alkaloid was dissolved in a given quantity of distilled water, with precisely sufficient hydrochloric acid to effect its solution.

1. Potassa.—Potassa produces in solution of hydrochlorate of veratria a copious, flocculent, dirty-white precipitate, which is not soluble in an excess of the reagent. If viewed immediately on precipitation by a low power of the microscope, it is seen in coagula, but if viewed after standing some minutes many short prismatic crystals will be seen amongst the coagula, which shortly disappear. The x}, grain of this veratria is most readily detected by this reagent, and with the microscope ;;55 may be easily recognized. The carbonate of the alkalies acts in the same manner as potassa.

2. Ammonia.—The reaction is the same as with potassa, but the precipitate is slightly soluble in an excess.

8. Nitric Acid—If concentrated nitric acid is brought into contact with this alkaloid it agglutinates into resinous-looking lumps of a dirty yellow color, which slowly dissolve in the acid. If the alkaloid is first moistened with water and a small quantity of nitric acid then applied, it exhibits a yellow tint, but on the addition of water forms a colorless solution.

4, Sulphocyanide of Potassium.—A flocculent white precipitate insoluble in excess of the reagent.

5. Chromate of Potassa.—A light yellow amorphous precipitate, insoluble in an excess.

6. Bi-Chromate of Potassa.—A copious, dirty yellow amorphous precipitate, insoluble in an excess of the reagent, but soluble in nitric acid.

7. Ferrocyanide of Potassium.—<A copious bluish-black, flocculent precipitate, soluble ifa small excess of the reagent is carefully added."

8. Ferricyanide of Potasstum.—An abundant greenish-yellow precipitate, soluble in an excess.

9. Lodide of Potassium.—-A dirty white amorphous precipitate, becoming a dirty greenish-white upon standing some time.

10. Lodine in Iodide of Potassium.—A copious reddish-brown amorphous precipitate, soluble in liquor potasse.

11. Bromine in Bromo-hydric Acid—A dull yellow amorphous precipitate.

12. Carbazotic Acid—A greenish amorphous precipitate, which upon standing a short time becomes a greenish-yellow.

' “This reaction takes place if an old solution is used, but if a new and pure solution is used there is no precipitate.”—W.

18. Bi- Chloride of Platinum.—A dirty yellow amorphous precipitate.

14. Bi- Chloride of Mercury.—A white precipitate. ©

15. Tannic Acid—A dirty white amorphous precipitate.

16. Terchloride of Gold—A canary yellow amorphous precipitate, insoluble in an excess of the reagent, and insoluble in acetic acid, except upon the application of heat.

17. Sulphuric Acid.—This test should always be applied to the alkaloid or its salts in a dry state. If a small portion of the alkaloid is touched with a drop of strong sulphuric acid no color is immediately developed, but in the course of a minute a yellowishred, and then a beautiful bright red color appears. This color will appear immediately upon touching the veratria with the sulphuric acid if the slide upon which it is placed is warmed. The color is not destroyed by heat, but it disappears after standing two or three hours; the color will disappear in fifteen minutes if a small crystal of bi-chromate of potash is stirred upon the mixture.

Professor Wormley has, by this reagent, detected s5}y5 of a grain of purified commercial veratria.

This last reagent—sulphuric acid—is the only one of all these that can be deemed decisively confirmatory of the presence of veratria; the other reagents are common to so many organic substances that they can only be regarded as confirmatory in connection with the action of sulphuric acid.

There is but one substance with which it would be at all likely to be confounded by this reaction of sulphuric acid, and that substance is salicine. Sulphuric acid produces a red color on solanine, narceine, papaverine, and piperine, but, as with salicine, the color is produced immediately upon the contact of the cold acid.

But the reaction of sulphuric acid on salicine and veratria differ, for whereas on salicine the color is immediately produced upon the application of sulphuric acid on a cold slide, we have seen that the color does not appear for a minute or more with veratria unless the slide or the acid is warmed.

The color produced is also different, for with veratria it is, for a moment, a yellowish, then a beautiful bright red, then an intense blood-red color; with salicine it is more of a purple red. There is the difference between the two colors that there is between bright arterial and venous blood. The color produced upon veratria lasts but two or three hours, while that produced upon salicine lasts double that time.

But the behavior with other reagents would definitely settle the point if doubts were excited.

In a correspondence with Geo. J. Scattergood, of Philadelphia, on this subject, he says: “ By treating commercial veratria with ether I have separated it into two substances. That portion insoluble in ether behaves with sol. of iodohydrarg. potass., and with tr. iodine, on a muriate boiling, and sal ammonia added while yet warm, differently from the way pure veratria does.

“ Veratria, soluble in ether, gives a beautiful pink-red or crimson color with sulphuric acid, and a butyric acid smell; the matter insoluble in ether gives a darker color, a greenish or brownish-red, and a musky odor.”

It will thus be seen that in following the experiments of Prof. Wormley with veratria obtained from Veratrum sabadilla, we have obtained almost identical results with the veratria we have made from Veratrum viride; and have thus confirmed Mr. Richardson’s observations, that the two alkaloids were identical in their chemical reactions.

Norr.—* Extraction of Veratrine by Ether and Chloroform.

‘1. The chloride of veratrine. One grain pure veratrine dissolved in 100 grains of water by the aid of hydrochloric acid, and then the solution agitated for several minutes with an equal volume of ether; the ether then drawn off and evaporated to dryness, leaves a residue of 3-100th grain of chloride of veratrine.

.“Qne grain of veratrine in 100 grains water, by the aid of hydrochloric acid, and agitated with an equal volume of chloroform, and the chloroform evaporated to dryness, leaves an opaque vitreous residue of 33-100th grains of chloride of veratrine.

“2. Pure veratrine. One grain of veratrine dissolved by hydrochloric acid in 100 grains of water, and the solution rendered slightly alkaline by potash solution, gives a copious white precipitate, so dense as to make the liquid almost gelatinous. If now the mixture be mixed with an equal volume of ether and agitated for several minutes, and then the ethereal solution evaporated to dryness, it leaves a transparent vitreous residue of 91-100th grain of pure veratrine.

““When one grain of veratrine is treated as above and agitated with an equal volume of chloroform, and the chloroform solution evaporated to dryness, it leaves a perfectly transparent vitreous residue of 97-100th grain of pure veratrine.”— From Ohio Med. and Surg. Journal, vol. xii., No. 6, p. 464, by Prof. Wormley.

DIVISION FOURTH.

DOSE AND MODE OF ADMINISTRATION.

By consulting other parts of this monograph it will be seen that the dose of the concentrated tincture (the formula for which is given in the first division of this section) varies in quantity and frequency of repetition according to the effect desired to be produced.

T shall be exceedingly explicit upon this point throughout the whole of the fifth section, and shall, therefore, need but few words at this place.

As an arterial sedative the dose, to an adult, may usually be from 2 to 8 minims, repeated every one, two, or three hours, according to the effect upon the pulse.

If it be deemed advisable to bring the patient promptly under its influence 8 minims may be given every hour until the pulse indicates its sedative influence, which will generally be felt before the third hour; it may then be repeated either in smaller doses or at longer intervals, but it will produce less unpleasant effects in small doses frequently administered, than in large ones at longer intervals.

Large doses are apt to produce vomiting, paleness, and alarming prostration, and the physician is frequently called in haste in consequence of the unpleasant effects of them. Nearly all. instances of alarm have been produced by large doses, and not by small ones frequently repeated. Large doses, also, do not so readily control the circulation, as excitement and vomiting supervene, and the pulse sometimes becomes thready, frequent, and irregular.

With children it is especially necessary to give it in small and frequent doses rather than in large ones at long intervals, and if administered in this manner alarming effects will seldom be produced.

Children, from the activity of the circulation and rapidity of excretion, will bear a rather larger proportional dose than adults ; thus a child eight years of age will bear about one-half the dose an adult will. To a child of that age 2 minims may be given asa first dose, and one minim may be repeated afterward every one or two hours according to its effect upon the pulse. Unless in very urgent 2 cases it is not advisable to bring the pulse more than 10 or 15 beats below the normal standard, and to do this it is but required to increase or diminish the dose according to the state of the pulse, and give it at intervals of one or two hours rather than at longer periods.

With adults a given number of minims may be put into a given number of teaspoonfuls of water, and one or more teaspoonfuls given at a dose.

With children it is more easily given in sweetened water, or sweetened water and orange juice, or syrup of tolu.

Section Third. Physiological Action On Animals

DIVISION FIRST.

EXPERIMENTS ELUCIDATING THE PHYSIOLOGICAL ACTION OF VERATRUM VIRIDE ON ANIMALS.

EXPERIMENT I.—Ten drops of the concentrated tincture put into a gelatine capsule, were passed down the throat of a mongrel dog weighing about twenty pounds; the dog had eaten nothing for six hours, and the pulse was beating 90 in the minute. In an hour and ten minutes after taking it, the dog vomited freely, and twice afterwards. In an hour anda half after the dose was given, the pulse was 60; in two hours and a half, 53. In four hours it had risen to 56; the dog seemed well, and ate heartily.

EXPERIMENT IJ.—Twenty drops of the same tincture were given to a dog who had been fasting for twelve hours. In an hour and seventeen minutes he vomited, and continued to strain and vomit for some time. At the expiration of two hours and a half, the same dose was repeated, the pulse then beating 61 in the minute. The dog, exhausted by the previous vomiting, lay down and did not attempt to stand up. In four hours from the administration of the first dose, the pulse was 29 in the minute, and the dose was again repeated. The retching was frequent, but nothing but a small quantity of viscid mucus and bile was thrown up. In five hours from the administration of the first dose, the pulse was 21, soft, creeping, and easily compressible. The pupils were fixed, but of ordinary size. They did not contract in strong light, but the lids were closed if anything was pointed at the eye. The dog would not move when struck with a switch. Six hours from the first dose, the twenty drops were repeated, the pulse being then 18, and intermittent. At the seventh hour there was great prostration, the retching continued, the pulse was irregular, intermittent, and easily compressed, and beating 17 in the minute. The dog would

* remain in almost any recumbent position he was placed, and his limbs were moved without an attempt at resistance. The lids would close if the eyeball was touched, otherwise they remained open; the eye had a fixed, staring, lack lustre look.

The dog was then left, and I did not see him again for twelve hours, during which time he drank two quarts of water. He seemed very feeble, and would come upon being called. The pulse was 149 and soft. He ate freely of meat, and later in the day seemed well, but sober, the pulse not exceeding 83 after his meal.

EXPERIMENT IIJ.—Two drachms of the same tincture in capsules, were enveloped in meat and given to a small dog. The pulse was 87. In two hours and twenty minutes he vomited some milk that had been taken just before the medicine, and threw off finally, all the contents of the stomach. In three hours the pulse was 389. After twenty-four hours, during which he was fed, he seemed quite well and lively.

EXPERIMENT IV.—The same dose was given in the same manner to a dog, and immediately afterwards a pint of melted lard was thrown into the stomach with a syringe. The pulse was 92. In three hours and five minutes the dog vomited, and the retching was prolonged and prostrating. In six hours the pulse was 44, and the prostration very great.

_ ExprrRtmMent V.—An ounce of the tincture, evaporated down to a soft extract and enveloped in a thin slice of meat, was given to a small dog who had eaten nothing for twenty-four hours. The pulse was 97, sharp and irritable. In thirty-eight minutes he vomited the meat with some fluid and mucus, and some of the extract. The pulse had fallen to 78. The vomiting continued, bringing up some frothy and bilious-looking matter. In two hours and a half the pulse was 55, and it did not at any time fall below 48, The prostration was less than in the two previous experiments. No doubt the greater part of the extract had been thrown