Parts used - Introductory remarks - Native species - Description of the root of Aconitum uncinatum - Chemistry of the root of Aconitum uncinatum - Clinical investigation of Aconitum uncinatum - The physiological action of Aconitum uncinatum - Description of the root of Aconitum fischeri - Analysis of Aconitum fischeri - A preliminary note of experiments with Aconitum fischeri, to determine its physiological actions - Comparison of the Actions of Aconitum Fischeri and Aconitum Napellus
PARTS USED.—The roots of Aconitum uncinatum Linn., and Aconitum Fischeri Reich.
Natural Order Ranunculaceae, Tribe Helleboreae.
INTRODUCTORY REMARKS.—The genus Aconitum has been celebrated from the earliest ages on account of the poisonous principle with which nearly all species of the family are possessed. [The Aκονιτον of the Greeks and Aconitum of the Romans are held to refer to the identical plant now mostly used in medicine, the Aconitum napellus.
In reference to the derivation of the word aconitum Dr. Chas. Rice writes us:
"The etymology is uncertain, and as there is no ancient name of the plant in other old languages, related to Greek and Latin, in which the same root occurs, we can only make a close guess. Pliny states that its name is derived from the fact that it grows εν ακοναις 'on steep rocks.' Theophrast refers it to the name of the city of Akonai, in Bithynia. Others refer it to ακονη (akone), 'whetstone,' 'sharp point.' There is no doubt it belongs to the Indogermanic root ak, 'to be sharp.'"] It is among the first recorded vegetable poisons used, and it is supposed to be that referred to by Pliny as being used for an arrow poison by the aboriginal Gauls. In India where some species are very virulent it is in common use to this day by the natives for this purpose.
To the ancients aconite was considered the most virulent poison, and has a prominent place in their mythology and legends. It was used to poison wild animals; hence the name "wolf's bane," by which it is now commonly known. ["The hunters which seeke after woolfes, put the juice thereof into rawe flesh, which the woolfes devoure, and are killed."—Gerarde (1597).]
The genus Aconitum is a native of mountainous countries, consisting of about twenty species, mostly found in the mountains of Europe and Asia. The species are specially liable to vary and on this account much confusion exists in their nomenclature. [Nearly thirty forms of the common European Aconitum napellus were mentioned by Seringe, in De Candolles Prodromus (1824), the most of which had been previously described as distinct species in Reichenbach's Monograph of the Genus.]
The flowers of Aconite are large and showy, and often an Aconite plant is found in flower-gardens. The color is usually blue, though a few European species have yellow flowers. The structure is peculiar and the flower of any of the species can be at once recognized by its odd shape. The petaloid calyx consists of five unequal sepals, the upper one (called the galea) much larger than the other, and hood-shaped or helmet-shaped. From this hood-shaped sepal resembling the cowl of a monk, the plant has received the common name Monk's Hood, by which it is generally known in English and American flower-gardens.
The root of Aconitum napellus, a common species of the mountains of Europe, was introduced into medicine by Störck, in 1762, and has ever since been a most important drug. Large quantities are imported and used in the United States, but none of our native species have been recognized by either Pharmacopoeia or Dispensatory.
NATIVE SPECIES.—With one exception the American species of Aconitum are found so rarely that they can not, excepting as homoeopathic remedies, be of any commercial importance. In the Western States, however, we have a species growing abundantly in many localities, and it is not unlikely that some day it may become an important source of the drug. [This plant has heretofore, as far as we can learn, never been investigated from a medical standpoint. The papers accompanying this article by Prof. F. B. Powers, on the chemical constituents, and by Prof. Roberts Bartholow on the medical properties, are made by our request. We trust they will turn attention to this plant, which deserves recognition.] In the Allegheny Mountains in the East we have two species.
Aconitum Uncinatum Linn.—This is a rare plant, found in rich, damp soil in the Allegheny Mountains. It is rare in Pennsylvania, but more common in Virginia, Maryland and further south. Its most northern station is Chenango county, New York, where it was discovered by Major Le Conte, early in the century, but has not been collected there since.
The stem is slender, weak and disposed to recline on other plants. It grows from two to five feet long. The leaves are borne on leaf-stalks from one to two inches long. They are smooth, deeply three (sometimes five) lobed; the lobes are acute and coarsely toothed.
The flowers appear late in summer and are bright blue. They are large and showy, and the plant is well worthy of cultivation in flower-gardens. The flowers are borne on peduncles about two inches long, from the axes of the upper leaves, and are usually in clusters of two or three. They have the characteristic odd shape of the genus. The galea is erect and conical, and beaked in front. The fruit is a cluster of usually three dry pointed pods containing numerous angular, rough seed.
FORMS.—This species, in accordance with the habits of the genus, is found in a number of forms. The plant grows in a territory where there are few botanists, and it is not commonly collected. A series of specimens from different localities would no doubt show a number of distinct forms.
De Candolle distinguishes two forms of the plant depending on the shape of the galea, one with the galea pointed, which he calls "var. Linnaeanum," the other with the galea obtuse, which he calls "var. Michauxianum."
The most remarkable form of the plant that has come under our notice was collected by Prof. Chickering, in July, 1880, on Little Roan Mountain, in North Carolina. The leaves are laciniately cut, and the flowers have a whitish tinge on the upper part. Prof. Chickering considers the plant Aconitum reclinatum, but as the chief character of that species is the pure white flowers, we can not but consider it a form of Aconitum uncinatum. [The following letter from Prof. Chickering, is of interest in connection with this form:
"In reply to your inquiries respecting Aconitum reclinatum, I have to say that I collected it on Roaring Brook, a noisy little stream running down the side of Little Roan Mountain, at an altitude of perhaps 2,500 feet. It was on July 20, 1880. I had noticed the leaves for some miles along the stream, and at last came upon a clump by the roadside in full flower. The flowering stalks were five or six feet high and made a very beautiful show.
"The main distinction between that species and our common Aconitum uncinatum is in the leaves, which are much more laciniately cut and divided, in the whitish tinge of the upper parts of the flower, and in the general habit and aspect of the plant.
"The botanies speak of it as being found in the high mountains of North Carolina, but I know definitely of no others besides Dr. Gray and myself who have collected it, and I found it in great demand among botanists. I collected perhaps a dozen stalks."
W. P. Conant, in allusion to Prof. Chickering's plant, says:
"We have also in the herbarium (of Department of Agriculture) a specimen collected on Roan Mountain by Prof. Chickering, and labeled Aconitum reclinatum. But the flowers are blue and the leaves seem cut somewhat different from those of Dr. Gray's own specimens."]
HISTORY.—This plant was known and named by Linnaeus in the second edition of the Species Plantarum (1762), and has been fortunate in escaping all synonyms except a single one, Aconitum scandens, a name given it by Muhlenberg.
A plant growing in various parts of mountainous Asia has been decided to be identical with the American plant. According to good authority the Asiatic species furnishes part of the root sold as "Bish," which is a very poisonous drug, and much used in the manufacture of the alkaloids. [Bish, Bis or Bisk, Indian Aconite root, Nepal Aconite, is according to the Pharmacographia, mainly derived from Aconitum ferox, but also from certain other poisonous species of Aconite, viz., Aconitum uncinatum, Aconitum luridum, Aconitum palmatum and Aconitum napellus. The main constituent of Aconitum ferox is a very poisonous alkaloid pseudaconitine, more virulent than aconitine.] If such is the case the root of the Asiatic plant differs from our native species, which according to our investigation has the characteristic alkaloid in a very small proportion. [A description of the root of Aconitum uncinatum and the result of its chemical and therapeutic investigation will be found after our botanical description of the other native species.
In this connection we call attention to the fact that different species of Aconitum do not exhibit in physiological action the effect that would be supposed to follow their close botanical relationships. Without apparent cause they are variably poisonous. The officinal species differs in virulence with climate and soil. The substance called aconitine varies markedly in value and physiological action as produced by different manufacturers, and as it is crystalline or amorphous. Dr. Charles Rice kindly loaned us the proof-sheets of "A Dictionary of the Economic Products of India," by George Watt, from which we condense the following:
Aconitum heterophyllum of India is largely eaten as a vegetable. The root is pleasantly bitter, and is by some considered as a mild antiperiodic and tonic, by others considered inert. The root of Aconitum palmatum "is very bitter, and contains a well defined bitter alkaloid, it has no poisonous properties." In considering these facts we are not surprised to find that Aconitum uncinatum, grown in the Allegheny Mountains of America, is comparatively inert and that the same species in mountainous India is a poison.]
Aconitum reclinatum Gray.—This species is confined to a very few localities, and is such a rare plant that it can never be of any interest as a medicine. It grows on a few mountain peaks of North Carolina and Virginia, and is found at an altitude of from four to five thousand feet. [The only habitats recorded are Grandfather and Negro Mountains, in Northeastern North Carolina, and Cheat Mountain in Virginia. though it no doubt grows on adjacent mountain peaks of the Southern Alleghenies.]
It selects damp and deeply shaded places. The stem is very weak and slender, from five to eight feet long, and when the plant is in flower it is generally prostrated. The flowers are white or cream colored, by which the plant can be at once distinguished from the preceding species. They appear in July.
This plant was discovered by Prof. Asa Gray, on an excursion to the mountains of North Carolina in the summer of 1841, and was described in the following year. [Dr. Gray first noticed the plant on Negro Mountain July 2, 1884. At that time it was only in bud, and he mistook it for the previously described species. On July 9, he found it growing and in bloom on Grandfather Peak, and the white flowers at once attracted his attention to it as a new species. It is described and named in the American Journal of Sciences, April, 1842 (Vol. XLII, 1st series), p. 34.
As far as we can learn Dr. Gray has the honor of being the only botanist that ever collected the plant.] There has never been any chemical or clinical investigation made of this plant, and there is no call for them.
Aconitum Fischeri Reich.—This is the only native species that can ever become of any commercial importance. It is abundant in the Rocky Mountains, and as it seems to possess the chemical properties of the imported root it may some day be an important source of the drug.
HISTORY.—There has been great confusion regarding the identity and nomenclature of this species.
The plant was first collected by David Douglas, in 1827, and forwarded by him to the Horticultural Society of London. It was not described until Hooker published his Flora Boreali-Americana (1833), where it was called Aconitum nasutum Fischer, being considered the same as a plant figured under this name by Reichenbach, in his illustrations of the genus. [Illustratio specierum Aconiti generis, Leipsig, 1823-7.] This plant was brought from Caucasus, Russia, and the name Aconitum nasutum was derived from Fischer's manuscript.
In 1838, when Torrey and Gray published the first volume of their Flora of North America, the plant had been again collected by Nuttall, in his then recent trip across the continent. It was described in the Flora under a name given it by Nuttall, Aconitum columbianum, in his manuscript description of the plant. Although there was doubt, at the time, of its distinction from Douglas' plant, yet it was also described in the Flora as Aconitum nasutum, taken from Hooker's Flora Borealis-Americana. As soon as the identity of the two plants was established, Nuttall's name was dropped, hence the plant has been known as Aconitum nasutum in most works on Western botany.
In very recent years Prof. Sereno Watson has decided that the plant is identical with Aconitum Fischeri, Reichenbach, which was figured in Reichenbach's work from a plant of Kamtschatka, and not with Aconitum nasutum of the same work. The close resemblance to the picture of Aconitum Fischeri was noted by Hooker at the time he first named the plant. Hence it is that in Watson's Flora of California and other very recent works the plant is called Aconitum Fischeri.
Aconitum Fischeri.—Description.—This plant is quite common along the banks of streams in the mountains of Western States. It is generally found near the tops of mountains and in mossy or boggy places. It usually grows near the water or in it, but never where the water is not fresh. It grows at an altitude of from 7,000 to 11,000 feet above sea level. The stem is erect and about three or four feet high, although in some favored situations it attains a height of ten feet. The stem is smooth except on the upper flowering portion which is covered with a short pubescence. The leaves are orbicular in outline and deeply three to five lobed; the segments are acute and coarsely and sharply toothed. The leaf stalks are two to six inches long.
The flowers appear in August or September and are borne in a terminal loose raceme. They have the usual odd Aconite shape, [The helmet is more arched and not quite as flat as shown in the engraving, which was made from a dried specimen. When the difference was discovered the plate had been made, and as the picture is a splendid one in every other particular, and the error a slight one that would only be noticed by a critical botanist, we did not think it would justify us to change the plate.] and can be recognized at once. They are usually of a deep blue color, but vary to nearly white in some instances. Sometimes plants are found with bronzed flowers.
FORMS.—The plant is found in a number of forms. These have never been closely investigated, but from what has been written we conclude that it is an extremely variable plant.
Cooper, in 1860, mentions that "two varieties have been collected in Washington," and Watson (1878) notes a small form from Southern Nevada.
DESCRIPTION OF THE ROOT OF ACONITUM UNCINATUM.—The tuberous root is of a brown, rusty color. It varies in size from one-fourth to one-half an inch in diameter at the top and resembles an oblique, short radish in appearance. It decreases rapidly in diameter, and tapers into a rootlet in from one-half to one inch from the top, few specimens attaining a greater length. Usually they are cone-shaped, as shown by our engraving, but occasionally are nearly cylindrical and blunt. The tuberous root grows close to the surface of the ground. Its natural position is oblique, as shown in our engraving. The terminal root often extends to a depth of from four to six inches, dividing and subdividing, and often several rootlets the size of a pin strike out from the main root.
The method of propagation is peculiar and interesting. The growing stem rises from the top of the oblique root, and in the spring of the year the root sends off near its top, and on the inner side, a runner which attains a length of from one to three inches. At its extremity is produced another tuberous root, which increases until it becomes the size of the parent root, growing obliquely in the same direction. When it has become full size the parent root begins to shrink, and finally it and the connecting runner die, and in the fall decay, leaving a scar on the new root. The new root is provided with a terminal bud, destined to produce the stem next year when the same act of reproduction is repeated.
As the runner is produced in the same direction each year the result is that the plant moves a step each season. Sometimes, though rarely, two offshoots are thrown out by the same plant.
Internally the freshly broken root is white, juicy and succulent; upon exposure of a fresh surface it changes to a pinkish hue. When fresh it is persistently bitter and retains the bitterness upon drying. It does not possess in the least the benumbing properties of aconitine, and as shown by the following chemical investigation it is free from that alkaloid. [In our opinion the identity of aconitine is as clearly established by the tongue as by a chemical investigation. We decided that it was absent by taste alone, and were borne out in our opinions by the chemical and clinical investigations.]
CHEMISTRY OF THE ROOT OF ACONITUM UNCINATUM.—(Written for this publication by Prof. Virgil Coblentz, Prof. of Materia Medica, Cincinnati College of Pharmacy).
To determine the constituents of the root we proceeded in the following manner:
A portion of the tincture made from the fresh root was acidulated with tartaric acid, one-half its bulk of water added, and the alcohol driven off by the heat of a water bath. The aqueous acid solution was then filtered, and this was shaken several times with absolute ether to remove the chlorophyll and fat. The ethereal residues when washed with carbon disulphide to remove coloring matter and waxes and the amorphous residue was found to consist of a bitterish glucoside. The acid solution was then agitated with ether after the addition of magnesium carbonate in slight excess, and after standing was separated, this process being repeated several times. The mixed ethereal solutions when evaporated left a very slight residue accompanied by a little coloring matter, and this was again dissolved in acidulated water and shaken with alkalies and ether. The residue (amorphous and white) was of a bitter and somewhat acrid taste, but entirely devoid of any of the benumbing or tingling sensations that would be caused by the presence of any traces of aconitine. This residue when dissolved in a small quantity of water acidulated with sulphuric acid gave affirmative reactions with the usual alkaloid reagents, but negative results with glucoside tests. The usual color reagents were applied to this (alkaloidal) substance with nothing at all distinctive worth noting. The minute quantity on hand as obtained precluded any further determinations as to its characteristics or proportion.
From these results we infer that the main constituents consist of a glucoside, and an acrid, bitter, amorphous substance of alkaloidal nature existing in minute quantity. Both of these are without distinctive characteristics.
CLINICAL INVESTIGATION OF ACONITUM UNCINATUM.—A tincture of the root of Aconitum uncinatum was made of the strength of officinal tincture of Aconite. This tincture was used in Randal's Island Hospital, New York, by W. E. Hallowell, M. D., House Physician, who prepared a table of the result for our publication. The patients were phthisis cases, in a rather advanced stage. Four patients were treated simultaneously. The commencing dose was two minims, which was increased one minim every two hours during one day, the final dose being seven minims. There was no effect.
The second day the commencing dose was ten minims, which was increased by two minims every two hours, the final dose being twenty minims. There was no effect.
The third day the commencing dose was thirty minims, which was increased by ten minims every two hours, the final dose being eighty minims; no result.
Observations were made on all the patients every hour, the record showing that no result followed even the large doses.
THE PHYSIOLOGICAL ACTION OF ACONITUM UNCINATUM.—(Written for this publication by Roberts Bartholow M. D., L. L. D., Professor of Materia Medica, General Therapeutics and Hygiene, in the Jefferson Medical College of Philadelphia.)
The preparation furnished by Prof. Lloyd, with which these experiments were made, has the strength of one-half that of official tincture of Aconite. The mode of administration was by sub-cutaneous injection, or by injection into the peritoneal cavity. The first experiments were directed to ascertain the general effects, and from the indications thus afforded, the inquiry was extended to the particular organs or tissues acted on by it. As a similarity of action was supposed to exist between the American and foreign Aconite, an attempt was made to determine this point.
First. The General Effects of Aconite.—Experiment 1.—Frog. Thirty minims of the solution injected into the peritoneal cavity caused apparently some weakness of the muscular system, as shown in the slowness of movements, and feeble jumping. The reflexes, corneal and muscular, appeared to be more active, and on irritation of the sciatic nerve the responses were prompt, the muscles contracting readily. On opening the chest the heart was found to be acting in the usual manner, and continued for the usual time.
Experiment 2.—Rabbit. Two drachms of the solution above given were injected subcutaneously. The effects corresponded to those described in the frog; that is, there were apparently general muscular weakness and heightening of the reflexes; but the circulation and the respiration continued at the normal rate. It does not appear to be at all toxic in these animals.
Second. Action on the Circulation.—Experiment 3.—After division of the medulla, two frogs, of medium size and weight, were placed side by side, their chests opened to expose the hearts. After the effects of the operation had subsided, in one the medicament was injected in the usual way, while the other remained undisturbed, as an experiment of control. Careful comparative observations did not disclose any difference in the rate and character of the cardiac movements. As the dose was sufficient to produce physiological effects, it may be concluded that the action of Aconitum uncinatum does not include the organs of circulation.
Experiment 4.—To ascertain the effect on the blood pressure.
Rabbit of medium size; the carotid connected with the manometer in the usual way. Two doses of two drachms each of the solution were administered subcutaneously. The results were entirely negative. There was no effect on the circulation, beside that due to any alcohol present in the preparation.
Commentary.—The experiments above narrated, are merely examples of a large number, made to ascertain the effects of Aconitum uncinatum. Its affinity to the Aconite of the Pharmacopoeia renders it an object of great interest from the physiological standpoint; but it is obvious that it possesses none of the powers of Aconitum napellus, or of Aconitum ferox. In fact it may be regarded as practically inert, although very large doses appeared to heighten a little the cutaneous and corneal reflexes of frogs, but to this result, under the circumstances, little importance should be attached.
The well-known tingling of the tongue and lips, caused by a minute quantity of the tincture of Aconitum napellus, or of Aconitum ferox, especially of the alkaloid aconitine, has been shown by Squibb to be a test of considerable delicacy. No similar impression is made by the preparation of Aconitum uncinatum submitted to examination. Studied with great care and by every available method, I was unable to discover that it possessed any property which can be utilized in medical practice.
DESCRIPTION OF THE ROOT OF ACONITUM FISCHERI.—Our engraving (Fig. 71) represents the average size of the roots obtained by us. It will be observed that they are cylindrical and taper at the lower extremity. They are, as a rule, of greatest diameter about one-fourth the distance below the top, approaching by a graceful curve the constriction that separates the stalk from the root. The parent root produces each season a small tuberous root (sometimes more), at the base of the stalk, which develops and increases during the season until it is of full size; then the stalk dies, the mother root shrinks and decays, the young root forms a terminal bud in anticipation of the coming season and also begins to send out the new root. Our engraving (Fig. 71) exhibits these several phases, the old, contorted, shriveled root being upon the right; the succulent, plump young root, fully developed, in the center, and with its terminal bud; the new root for next season upon the left.
The development of the root of Aconitum Fischeri is the same as that of the European drug Aconitum napellus. Those who are acquainted with the aconite root of commerce will recognize its close resemblance to our figure. It differs from the Aconitum uncinatum which has the young root developed at some distance from the parent root.
The taste of the root of Aconitum Fischeri is bitter, and it benumbs the tongue like the officinal Aconite. Its chemical properties have been studied by Prof. F. B. Power, whose report we introduce verbatim, as follows:
ANALYSIS OF ACONITUM FISCHERI.—(Instituted for this publication by Prof. F. B. Power, assisted by Henry G. Ruenzel).
The material employed for this investigation consisted of the coarsely comminuted root, which was received in a bottle containing a small quantity of alcohol with which it had been digested. The root and liquid were transferred to a flask, about 200 cubic centimeters of alcohol, acidulated with sulphuric acid added and digested on a water-bath for about twelve hours. It was subsequently allowed to macerate for about a day and a half, the alcoholic liquid filtered off, and the root washed upon the filter with about fifty cubic centimeters of alcohol. The residual root, after drying by exposure to the air, weighed twenty-two grams, the original weight of the root being forty-four grams.
The root extracted by alcohol was subsequently digested in the water-bath for twelve hours with water acidulated with sulphuric acid, then allowed to macerate over night and filtered. The filtrate afforded no reaction with alkaloidal reagents, thus indicating that any alkaloid present had been completely extracted by the acidulated alcohol. From the latter liquid the alcohol was removed by distillation and final evaporation, and to the resulting aqueous liquid sufficient water was added to bring the volume to 100 cubic centimeters. This was divided into two equal portions of fifty cubic centimeters each, and having been found to afford an abundant precipitate with alkaloidal reagents, it was treated as follows:
One portion was transferred to a separating funnel, made alkaline with ammonia water, and then shaken with ether. The ethereal liquid upon evaporation afforded a residue which gave the characteristic color reactions for aconitine with concentrated sulphuric and phosphoric acids, although not so decidedly as pure aconitine, which was doubtless to be attributed to small amounts of adhering impurities; when dissolved in alcohol, however, and applied to the tongue, it produced the characteristic tingling sensation and numbness.
The other portion of fifty cubic centimeters of liquid was employed for the quantitative estimation of the alkaloid, and this was accomplished volumetrically by means of a standard solution of potassio-mercuric iodide containing 13.546 grams of mercuric chloride and 49.80 grams potassium iodide in one liter, and therefore 1-20 normal. According to the investigations of Dragendorf, one cubic centimeter of this solution corresponds to 0.0269 gram aconitine, [Die chemische Werthbestimmung einiger starkwirkender Droguen, St. Petersburg, 1874.] with acceptance of the formula of Duquesnel C27H40NO10. [Journe de Pharm. et de Chem, (4 ser) , T. 14, p. 94.] It was found that 6.3 cubic centimeters of the above 1-20 normal solution were required to completely precipitate the alkaloid, which would therefore correspond to 0.16947 gram of aconitine, or 0.33894 gram in the entire amount of material employed.
This clinical investigation of Prof. Power is almost conclusive evidence that our Aconitum Fischeri contains an alkaloid, or alkaloids, that will prove of therapeutic value. In consequence of the small amount of the drug at our disposal, Prof. Power was unable to identify individual alkaloids as carefully as he would have been pleased to do, and considering the interesting physiological report of Prof. Bartholow, we regret very much that this is the case. Aconitum Fischeri undoubtedly contains the alkaloid aconitine, but it is associated with other proximate principles that, as shown by the physiological investigations of Prof. Bartholow, modify its action in a most interesting manner. The following paper, in his usual thorough manner, presents the results of his work with a portion of the tincture like that sent to Prof. Power.
A PRELIMINARY NOTE OF EXPERIMENTS WITH ACONITUM FISCHERI, TO DETERMINE ITS PHYSIOLOGICAL ACTIONS.—(Written for this publication by Roberts Bartholow, M. D., L. L. D., Professor of Materia Medica, General Therapeutics and Hygiene, in the Jefferson Medical College of Philadelphia.) [Dr. Bartholow desires to thank Dr. A. P. Brubaker, Demonstrator of Physiology and Experimental Therapeutics, for valuable assistance in performing the experiments.]
The preparation used in the following experiments is a tincture made by Prof. J. U. Lloyd, having the strength of the officinal tincture of Aconite. The alcohol it contained was evaporated on a water bath.
Cold-Blooded Animals.—Experiment 1.—Frog of medium size. At 4 P. M. thirty minims were injected into the abdominal cavity. In two minutes the frog gagged violently, opened the mouth widely, and with the fore feet wiped off the tongue repeatedly. At the same time a quantity of mucus was discharged from the mouth. This condition persisted for several hours, the intervals between the acts of gagging growing longer, however, and they, also, lessened in severity. At the end of three hours the frog seemed torpid, and could not clear the surface in attempting to jump. The sensibility and the cutaneous and corneal reflexes were not lessened. Irritation caused prompt muscular movements so long as the power of motion remained.
At 9 P. M. paralysis was complete, and the frog seemed to be lifeless. At 7 A. M., on the following morning, the same conditions existed. At 9 A. M. the chest was opened, and the heart found beating strongly and rhythmically at thirty-two per minute, and continued for some hours longer.
This experiment, several times repeated, yielded uniform results.
Experiment 2.—Frog of medium size. Isolated the sciatic, and ligatured the thigh to cut off the circulation from the limb below. When, after the administration of the solution, the paralysis was complete, mechanical, chemical and electrical irritation of the sciatic, caused active movements of the unpoisoned muscles. Faradic stimulation of the opposite sciatic, and of the muscles at any point, caused active contractions.
From this experiment we conclude that this drug does not impair the irritability of the motor nerves, or the contractility of the voluntary muscles, and that the paralysis caused by it is centric in origin.
That the sensory nerves remain unaffected by it is established by two facts: the frog, in experiment I, made attempts to get out of the way of an irritation, until the paralysis became complete, and when this condition was reached, faradic excitation of the sciatic caused rapid and stronger action of the heart, when its movements had almost ceased.
Experiment 3.—Frog of medium size. Heart exposed in situ; the pneumogastric isolated. Thirty minims of the solution injected as before. When the effects first became manifest, but a feeble response was obtained on Faradic stimulation of the vagus; the heart was slowed but not arrested in movement when a strong current was applied. When the maximum effect of the drug was attained, a strong current did not affect the movements of the heart in any way; in other words, the vagus had lost its irritability-its power of response to irritation.
Warm-Blooded Animals.—Experiment 4.—To determine the general effects of the Aconitum Fischeri.
Rabbit; medium size. Half a drachm of the preparation used in the preceding experiment was thrown into the jugular vein. Paralysis of the extremities followed in a few seconds, the respiration became exceedingly labored, and in five minutes death ensued by failure of the respiratory muscles. On opening the chest the heart was found in strong and rapid action, and continued so for sometime afterwards.
Experiment 5.—Rabbit. The carotid was connected with the manometer and revolving cylinder in the usual way. One drachm of the Aconite solution was thrown into the abdominal cavity. In a minute the characteristic paresis of the respiratory muscles occurred, and at the end of five minutes they were completely paralyzed, and death ensued.
There was no decline of the blood pressure until the failure of respiration. The tracing taken exhibits an increased amplitude of the pulse wave, and the interval between the beats was somewhat lengthened. Faradic excitation of the pneumogastric had no effect on the cardiac movements.
Experiment 6.—Rabbit. The vagus exposed and prepared for faradic stimulation. Injected a drachm of the solution into the peritoneal cavity. The same effects as in the preceding experiment promptly followed. When the maximum action was attained, the vagus was stimulated by a strong Faradic current, but the movements of the heart were not arrested-were not, indeed, in any way affected.
Commentary.—A close correspondence is seen in the effects of Aconitum Fischeri on cold and warm-blooded animals, except as to the rate of movement. It acts more speedily on warm-blooded animals, and also relatively to dose, more powerfully. As respects the character of the actions there is identity. These experiments authorize the following conclusions:
Aconitum Fischeri is a paralyzer of motility, but it does not impair the contractility of muscles, or the irritability of the motor nerves. Its action is central, not peripheral.
It does not affect sensibility or the reflexes until all manifestations of motor activity cease.
It does not paralyze the heart, but by removing the inhibition permits a more active movement of the organ. It paralyzes most completely the vagus so that the strongest stimulation causes no response.
Death ensues by paralysis of the respiration, the heart continuing in action for sometime after respiration has ceased.
Experiment 7.—To determine the effect of the Aconitum Fischeri on the mucous membrane, I placed a large drop near the extremity of my tongue. In a minute the tingling which is so character. istic a symptom of Aconitum napellus was perceived, and it then rapidly increased, but did not attain its maximum for an hour. I then tested the state of the sensibility of the tongue at this point with the aesthesiometer, and found that the perception of the two points was as acute as at the unaffected parts of the mucous membrane. The pain sense was as little affected as the tactile sense. Pricking with the point of the aesthesiometer caused as acute a sense of pains in the area occupied by the tingling as elsewhere. At the end of two hours the tingling was hardly abated in any degree.
Experiment 8.—To ascertain if there be an antagonism between Aconitum Fischeri and strychnine.
Frog; same size as those used in the foregoing experiments. As the action of the agent is comparatively slow in frogs, to save time, I injected one drachm of the solution, being twice the quantity used in the other experiments. The paresis began in fifteen minutes, and at the expiration of an hour paralysis was complete, and all reflex movements had ceased. I then injected one-fiftieth of a grain of sulphate of strychnine.
In one hour after the injection of the strychnine, slight reflex contractions of the legs could be induced by tapping them smartly. Scratching the skin of the abdomen and of the thighs, induced somewhat more active reflex movements. There being no increase in the effects of the strychnine, and three hours after the first dose, a second one of one seventy-fifth of a grain was administered. This distinctly increased the cutaneous reflex, for a little scratching of the skin now caused more prompt and extensive movements. The action of the strychnine did not increase, and after eight hours, no external manifestation of life was apparent, the frog lying limp, extended at full length, and dry on the upper part of the body. The slight impression made by the large quantity of strychnine given, is the more remarkable, since frogs are exceedingly susceptible to the action of this agent, the one three-hundredth of a grain sufficing to cause active tonic Spasms.
Commentary.—That there is an antagonism between Aconitum Fischeri and Strychnine is evident; but the extent of it remains to be determined. That these agents are opposed in the spinal actions of each, would, from a priori considerations, be considered probable; experiment demonstrates that such is the fact. That the aconite will antagonize the lethal effects of strychnine rather than the opposite, will, no doubt, be shown by future investigations.
Comparison of the Actions of Aconitum Fischeri and Aconitum Napellus.—Notwithstanding the botanical affinities and, in some respects, the physiological, there are marked and fundamental differences.
Aconitum napellus affects sensibility, and lowers the irritability of the sensory nerves. Aconitum Fischeri does not affect the tactile, or pain sense, although it causes the characteristic tingling, and it does not affect the irritability-the power to perceive and transmit peripheral impressions-of the sensory nerves.
Aconitum napellus paralyzes the end organs of the motor nerves, the trunks, and ultimately the motor portion of the cord. Aconitum Fischeri does not affect the contractility of muscles, or the irritability of the motor nerve, but paralyzes the motor centres of the cord.
Both cause death by paralysis of respiration.
They affect the heart in opposite modes: Aconitum napellus stimulates the vagus roots, and slows the heart, while Aconitum Fischeri paralyzes the pneumogastric and increases the force and number of the cardiac pulsations. Aconitum napellus, after a brief, stimulating action, paralyzes the vasomotor center in the medulla, and greatly lessens the blood pressure. Aconitum Fischeri rather stimulates the vasomotor center, and does not lower the blood pressure.
Many points regarding the actions of Aconitum Fischeri remain to be determined. The writer intends to continue his study, but meanwhile submits to the readers of this journal this preliminary note, which contains sufficient facts to stimulate those interested in such work to undertake further investigations. To the practical therapeutist, Aconitum Fischeri offers a most interesting and fruitful subject for investigation of its remedial powers.
Drugs and Medicines of North America, 1884-1887, was written by John Uri Lloyd and Curtis G. Lloyd.