Liriodendron Tulipifera. Tulip tree, cont'd.

Continued from previous page.

Actions of hydrochlorate of tulipiferine - Homoeopathic uses - Pharmaceutical and medical references

A STUDY OF THE ACTIONS OF HYDROCHLORATE OF TULIPIFERINE.—(Written for this publication by Prof. Roberts Bartholow, M. D., LL. D., Professor of Materia Medica, General Therapeutics and Hygiene, in the Jefferson Medical College of Philadelphia.)—I am indebted to Prof. J. U. Lloyd for a solution of Hydrochlorate of Tulipiferine, an alkaloid recently separated by him from Liriodendron Tulipifera, and to which I have ventured to assign the name above given. A principle called Liriodendrin was obtained by Emmet so long ago as 1831, but it is no longer doubtful that this is not the active principle of the tree. At all events, no investigations of the physiological properties of any constituent of the tree has been undertaken up to the present. Indeed, from the current opinions regarding its therapeutical powers, it is evident that it has not been supposed to possess any considerable activity. Although large doses, relatively, of this alkaloid are required to produce decided physiological effects, it is far from being an inactive substance. An eighth of a grain of Prof. Lloyd's alkaloid affects large frogs, and one grain is sufficient to develop full physiological actions in medium rabbits. The exact lethal dose has not yet been determined, but it is but little above the quantities just named.

General Effects.—In the dose of one-eighth grain it causes paresis, muscular trembling, convulsions of a partly clonic, partly tonic character, heightened cutaneous and ocular reflexes, followed by stupor, increasing paralysis, and finally complete suspension of motility and sensibility. When all the phenomena of life have then apparently ceased, if the chest of the frog is opened, the heart is found to be in slow but rhythmical and sustained action.

In the dose of one-quarter grain administered subcutaneously, the action follows promptly—in twenty minutes—and then the convulsions have a more decidedly tonic character, followed by temporary trembling. The cutaneous reflex is then so much heightened that the faintest impression on the skin is immediately followed by a tonic convulsion, temporary rigidity, and then relaxation succeeds, the limbs remaining extended. After an hour or two the convulsions cease, there is complete muscular relaxation, and the frog seems lifeless-but on opening the chest, the heart is found acting in slow but strong rhythmical contractions, as above stated.

Action on the Peripheral Nerves.—When the sciatic is isolated, it is found that after the action of the medicament begins, the nerve responds to mechanical, chemical and electrical stimuli. As the effect continues and deepens, however, the nerve becomes less and less excitable; but the power of response seems never to be entirely lost. The excitability of the sensory nerves declines pari passu with the diminution of the motor, and is at last finally extinguished—for no amount of irritation at last causes any direct or reflex action. Whilst the motorial power is lessening, the muscles continue to respond to the various stimuli to the latest manifestation of any vital action. It follows from these facts that the paralyzing power of Tulipiferine is centric chiefly.

As respects the convulsions, they are found to be centric or spinal in origin, also. If a frog be pithed (i. e., spinal cord destroyed), no convulsions can be produced by any dose.

Action on the Pneumogastric Nerve and Heart.—After division of the medulla oblongata, the heart is exposed in situ, and when the disturbance caused by this procedure has ended, the cardiac pulsations are counted, and the rhythm compared with the metronome beating seconds. As the effect of the medicament deepens after the convulsions have ceased, the pneumogastric becomes less and less excitable on faradic stimulation, until at length no action is had from even a powerful current. The muscular tissue of the heart remains excitable up to its physiological death, for after the final cessation of its movements, it can be excited to contraction by a faradic current, and for a time by merely mechanical stimulation. In these effects of tulipiferine, there is some resemblance to the actions of atropine, but more differences. When the effects of tulipiferine begin, the action of the heart is increased in the number of its pulsations, in correspondence with the decline in the excitability of the vagus, but when the vagus ceases to be excitable, the cardiac pulsations diminish in number, but gain in force, the rhythm being preserved. This apparent paradox seems to be explained by the action of the alkaloid on the accelerator apparatus. A coincident loss of the stimulus derived from the accelerator nerves, and of the inhibitory action of the vagus, is, no doubt, the cause of this apparent anomaly.

Tulipiferine has some action on the cerebrum. In warm-blooded animals, a soporose state, deepening into coma, succeeds to the convulsant action. If a barely lethal quantity is administered to a frog, the animal will lie extended, apparently lifeless for twenty-four hours, and probably longer. If, whilst in this state of muscular relaxation and stupor, an irritant be applied, attempts at motion will be made; but when the irritant is withdrawn, the condition of stupor is resumed. Before death, however, complete sensory paralysis takes place, when no response to irritation is made, and that life still exists can be ascertained only by opening the chest to find the heart in action. The sustained and rhythmical action of the heart is even then manifest; the contractions, although occurring infrequently, are still forcible. It should have been mentioned above that the auricles are the last to suspend action.

This study of tulipiferine serves to explain the former empirical uses of Liriodendron. In Rush's time it had reputed virtues as a tonic, as a supporting medicine in fevers, and antiperiodic properties were ascribed to it. The alkaloid will, no doubt, be found useful whenever a tonic to the heart is required. If my conclusions are justified by further studies, and by the observations of others, its applicability to certain phases of cardiac weakness will be peculiarly apt. It is not a powerful alkaloid, and can hardly be dangerous to use, because of the retention by the cardiac muscle of its irritability when a lethal dose has been administered.

THE HOMOEOPATHIC USES OF LIRIODENDRON.—(Written for this publication by Edwin M. Hale, M. D., Emeritus Professor of Materia Medica and Therapeutics in the Chicago Homoeopathic College.)—During my early practice in the country, I observed that the people used a decoction of the bark of this tree, or a tincture of it macerated in whiskey, as a domestic remedy in some intestinal disorders, such as diarrhoea, colic and worms.

After testing on myself in health the alcoholic tincture, and finding that it seemed to be a stimulant to the gastric and intestinal mucous surfaces, also as a nerve stimulant, I began its use in certain chronic intestinal catarrhs, accompanied by indigestion, flatulence and pain. In many cases it appeared to act better than Leptandra. It appeared to act best in nervous women and children. The intestinal irritation, under its use, soon disappeared, and the semi. fluid, undigested stools disappeared. It stimulated the appetite, and aided in the assimilation of food. In that class of infantile disorders, usually attributed to worms, particularly when attended by remittent, irritative fever, it seemed to act well, although no worms were expelled.

In doses of one drachm it often appeared to stimulate the gastric functions too much, but when given in doses of five to ten drops, no unpleasant effects followed. For children, my usual plan was to put five or ten drops in one-half glass of sweetened water, and order a teaspoonful of this, to be given every two or three hours.

During the last ten years I have not used it, but I believe that it will be found a useful remedy when its physiological action is accurately investigated.

PHARMACEUTICAL AND MEDICAL REFERENCES TO LIRIODENDRON TULIPIFERA.

1787.—Materia Medica Americana, David Schoepf, p. 90.

1802.—Collections for a Materia Medica of the United States, B. S. Barton, Part II., p. 14 (edition 1810).

1811.—The American Medical Lexicon (not paged).

1818.—The American Dispensatory, Coxe, 4th edition, p. 328.

1820.—House Surgeon and Physician, Hand, p. 234.

1821.—Supplement to the Pharmacopoeia, London, p. 148.

1822.—Treatise of the Materia Medica and Therapeutics, Eberle, Vol. I., p. 279.

1824.—Elements of Therapeutics and Materia Medica, Chapman, Vol. II., (3d edition), p. 446.

1827.—The Medical Companion, or Family Physician, Ewell, p. 710.

1829.—Manual of Materia Medica and Pharmacy, Edwards & Vavasseur, p. 175.

1830.—An Introduction to the Natural System of Botany, Lindley, p. 24.

1830.—Pharmacopoeia of the United States, (Philadelphia), p. 34

1830.—Pharmacopoeia of the United States, (New York), p. 43

1830.—Medical Flora and Botany of the United States, Rafinesque, Vol. II., p. 239.

1831.—American Journal of Pharmacy, Vol. III., p. 5.

1832.—An Improved System of Botanic Medicine, Howard, Vol. II., p. 334, (and other editions).

1833.—The American Practice of Medicine Beach Vol. III., p. 115.

1833.—Dispensatory of the United States of America, Wood & Bache, (and subsequent editions) p 392.

1833.—Prodome of a Work to Aid in the Teaching of the Vegetable Materia Medica, W. P. C. Barton, p. 67.

1834.—American Journal of Pharmacy, p. 286.

1834.—A System of Materia Medica and Pharmacy, Murray, (6th edition), p. 153, (and other editions),

1835.—Medical Botany, or, Sick Man's Friend, Sanborn, p. 67.

1838.—Chemistry of Organic Bodies, Thomson, p. 835.

1838.—Flora Medica, Lindley, p. 23.

1840.—Pharmacopoeia of the United States, p. 46.

1840.—Pharmacopée Universelle, Jourdan, p. 542.

1841.—A Practical Edition of Materia Medica, Bell, p. 306.

1843.—General Therapeutics and Materia Medica, Dunglison, Vol. II., (ad edition), p. 87.

1845.—The Practice of Medicine on Thomsonian Principles, Comfort, p, 468.

1846.—The Elements of Materia Medic and Therapeutics, Pereira, p. 744.

1847.—Materia Medica and Therapeutics, Royle, p. 248.

1847.—The Botanico-Medical Reference Book, Biggs, p. 548-

1847.—Medical Botany, Griffith, p. 98.

1848,—Dispensatory and Formula, Mayne, (Griffith's revision), p. 276.

1848.—Medicinal Plants of New York, Lee, p. 7.

1849.—Medicinal Plants of South Carolina, Porcher, (Report Am. Med. Assoc.), p. 696.

1849.—Elements of Materia Medica and Therapeutics, Kost, p. 446.

1850.—Pharmacopoeia of the United States, p. 51.

1850.—Medicinal Plants of the United States, Clapp, (Report Am. Med. Assoc.). p, 727.

1852.—The Eclectic Dispensatory, King and Newton, (and subsequent editions of American Dispensatory), p. 245.

1857.—Materia Medica and Therapeutics, Mitchell, p. 565.

1860.—Pharmacopoeia of the United States, p. 60.

1860.—Journal of Materia Medica, Bates & Tilden, p. 161.

1870.—Eclectic Medical Journal, Cincinnati, p. 205.

1870.—Report of Botanical Survey of Southern and Central Louisiana, Featherman, p. 32.

1870.—Pharmacopoeia of the United States, p. 39.

1872.—Pharmacopoeia Homoeopathica Polyglotta, p. .89.

1873.—Pharmaceutical Lexicon, Sweringen, p. 251.

1873.—Journal of Materia Medica, Bates & Tilden, p. 1.

1873.—Druggists' Circular, p. 58.

1878.—Dispensatory and Pharmacopoeia of North America and Great Britain, Buchanan and Siggins, p. 193.

1881.—Specific Medication, Scudder, p. 169.

1882.—Dictionary of Economic Plants, Smith, p. 421.

1884.—The National Dispensatory, Stille and Maisch, 3d edition, p, 929.

1884.—Companion to the United States Pharmacopoeia, Oldberg and Wall, p. 655.

Drugs and Medicines of North America, 1884-1887, was written by John Uri Lloyd and Curtis G. Lloyd.