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Strophanthus Hispidus: Its Natural History, Chemistry, and Pharmacology

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Strophanthus Hispidus: Its Natural History, Chemistry, and Pharmacology ( 955 ) XXI.—Strophanthus hispidus: its Natural History, Chemistry, and Pharmacology. By THOMAS K. FRASER, M.D., F.K.S., F.R.S.E., F.R.C.P.E., Professor of Materia Medica in the University of Edinburgh. PART I.'—NATURAL HISTORY AND CHEMISTRY. (Plates I.-VII.) (Read 4th February 1889.) CONT ENTS. PAGE PAGE HISTORICAL INTRODUCTION, 955 B. CHEMISTRY— 1. Seeds— A. NATURAL HISTORY— Composition; Ether Extract; Alcohol 1. Use in Africa as an Arrow-Poison, and Extract, its Characters, Constituents, Description of Arrows, 960 and Reactions; Absence of an Alka- loid ; Presence of a Glucoside, 993 2. Botanical Description— Strophanthin; its Preparation, Charac- General Description, 975 ters, Composition, and Eeactions, . 1008 Description of Root, Stem, Leaves, Strophanthidin; Kombic Acid, 1017 Flowers, Follicles, and of Seeds and 2. Composition of other Parts of the Plant— other contents of the Follicles, 977 Comose Appendages; Pericarp; Leaves; Dehiscence of Follicles and Dissemi- Bark; Boot, 1018 nation of Seeds, . 990 Explanation of Plates I.-VIL, 1025 HISTORICAL INTRODUCTION. The preliminary notices published by me in 1870 and 1872, on the action arid chemistry of Strophanthus, indicated that it was likely to prove of value as a therapeutic agent; and so early as the year 1874, I had applied the substance in a few cases to the treatment of disease. Before sufficient data, however, had been obtained to justify any conclusions regarding its value as a therapeutic agent, the observations were interrupted by my leaving Edinburgh to occupy a public office in England, in connection with which it was impossible to conduct observations on the treatment of disease. In 1879, oppor- tunities were again afforded to resume the interrupted observations, and results con- firmatory of the anticipations which had been raised by the earlier physiological observa- tions were gradually collected. The publication of a few of these results at the Cardiff meeting of the British Medical Association in 1885* has led to Strophanthus gaining a wide recognition as an important therapeutic agent, and to the production of numerous papers dealing with its botany, chemistry, pharmacology and therapeutics, not only in this country, but also in the continent of Europe and in America. In this paper I propose to give, with greater detail than has been attempted in the * British Medical Journal, vol. ii., 1885, p. 904. VOL. XXXV. PART IV. (NO. 21). 7 G 956 DR THOMAS R. FRASER ON STROPHANTHUS HISPIDUS. previous communications, an account of the observations I have made on the general natural history, the chemistry, and the pharmacology (or physiological action) of Strophan- thus. Before doing so, it may be desirable to state what knowledge existed with regard to these departments of its study and consideration previously to the publication of my papers of 1870 and 1872; to reproduce some of the leading statements contained in these papers ; and to indicate the extent to which the knowledge regarding Strophanthus was increased during the period of fifteen years which elapsed between the publication of my paper of 1870 and of my subsequent paper read before the British Medical Association in 1885. Previously to the publication of my preliminary paper of 1870, the knowledge regard- ing Strophanthus consisted of several botanical descriptions of the plant; of notices by travellers of its use by African tribes, who had discovered its poisonous action, and had employed it as an arrow-poison in the chase, and apparently also in warfare; and of a few brief references to some points relating to its physiological action. Interest was first attracted to the physiological action of this substance by the intro- duction into Europe of a few specimens of fruits and seeds reputed to be the source of a remarkable arrow-poison used in several parts of Africa, and termed in some districts the Kombe and in others the Inee poison. The physiologists who first examined the properties of this poison seem to have been SHARPEY, and HILTON FAGGE and STEVENSON of London, and PELIKAN of St Petersburg. SHARPEY'S experiments were made in 1862-63, but they were not published, as before his investigation had been completed my preliminary notice of 1870, briefly descriptive of the general results I had then obtained, was communicated to this Society, and, much to my regret, led SHARPEY to refrain from publishing his observations, as they entirely agreed with those contained in my paper. From the notes of his experiments, which he afterwards very kindly sent to me, it is apparent that SHARPEY had determined that the action of Strophanthus was characteristically that of a cardiac poison. On the 18th of May 1865, HILTON FAGGE and STEVENSON stated, in a note appended to a paper communicated to the Eoyal Society of London, on the " Application of Physio- logical Tests for Certain Organic Poisons,"* that the Manganja arrow-poison, obtained during the Zambesi Expedition by Sir JOHN (then Dr) KIRK, acts as a" cardiac poison." By this expression they imply an action on the frog's heart of the same kind as that produced by digitalin, Antiaris toxicaria, Helleborus viridis and niger, Scilla, and certain other poisons ; and, especially, that the heart is stopped with the ventricle " rigidly contracted and perfectly pale." In the same year, on the 5th of June, PELiKAN.t in a note communicated to the Academy of Sciences of Paris, pointed out that an extract obtained from the seeds which yield the Inee or Onage arrow-poison acts on the frog's heart in the same way as digitalis * Proceedings of the Royal Society, vol. xiv., 1865, p. 274. t " Sur un nouveau poison du coeur provenaiit de l'Inee ou Onage, et employe au Gabon (Afrique Ocoidentale) comme poison des fleches " (Comptes Bendus de VAcade'mie des Sciences, tome lx., 1865, p. 1209). DR THOMAS R. FRASER ON STROPHANTHUS HISPIDUS. 957 and other similar cardiac poisons, but with greater activity. The heart's beats were quickly arrested, with the ventricle in systole and with the auricles distended. This effect is attributed by him to an action on the nerve structures of the heart. He also states that his experiments were confirmed by VULPIAN. PELIKAN obtained the seeds from the Colonial Exhibition held in Paris in 1865, to which they had been sent by M. GRIFFON DXJ BELLAY, a surgeon in the French Naval Service, who had obtained them in the Gaboon district of West Africa, where they are used by an elephant-hunting tribe (Pahouins) to poison their small bamboo arrows. In 1869, a few specimens of ripe follicles were presented to the Materia Medica Museum of the University of Edinburgh by the Rev. HORACE WALLER, who had been a member of the Oxford and Cambridge Universities Mission of 1861-64, superintended by the late Bishop MACKENZIE, with whom had been associated, during the operations of the mission between the Eiver Shire and Lake Shirwa, the famous traveller LIVING- STONE and the enterprising botanist KIRK. The follicles were sent with the information that the seeds contained in them constituted the Kombe arrow-poison of South-Eastern Africa. Mr WALLER informs me that, at his suggestion, they had been brought to this country by Mr E. D. YOUNG, R.N., when he went to Africa in 1867, to clear up the story of LIVINGSTONE'S murder. Sir ROBERT CHRISTISON placed these follicles at my disposal for examination, and as in the course of time the insufficient material which they afforded was supplemented by some additional follicles sent to me by Professor SHARPEY and, afterwards, by Mr JOHN BUCHANAN, I was enabled to determine the most important facts in the pharmacological action, as well as in the chemistry of the substance, some of which were communicated to this Society in February 1870, in the form of a preliminary notice, and published in the Proceedings of that year,* and also, with a few amplifications, in the Journal of Anatomy and Physiology of 1872.1 While the investi- gation was in progress, Sir DOUGLAS MACLAGAN received from Sir JOHN KIRK a poisoned arrow, obtained from the same district of Africa as the follicles; and with this arrow I was enabled to determine that the poison possesses the same action as the seeds contained in the follicles, and thus to confirm the discovery already made by KIRK of the source of the arrow-poison.} My experiments were made on cold-blooded animals and on birds and mammals ; and the administration was effected by subcutaneous injection, and by introduction into the * Proceedings of the Royal Society of Edinburgh, vol. vii., 1869-70, pp. 99-103. t Journal of Anatomy and Physiology, vol. vii., 1872, pp. 140-155. % In a recently written letter (31st Oct. 1888) Sir JOHN KIRK thus graphically describes the discovery he had made in 1861 of the plant from which the Kombe poison is obtained :—" The source of the poison, namely, Strophanthus Kombe', was first identified by me. 1 had long sought for it, but the natives invariably gave me some false plant, until one day at Chibisa's village, on the river Shire, I saw the ' Kombe,' then new to me as an East African plant (I had known an allied, or perhaps identical, species at Sierra Leone (1858), where it is used as a poison). There climbing on a tall tree it was in pod, and I could get no one to go up and pick specimens. On mounting the tree myself to reach the Kombe pods, the natives, afraid that I might poison myself if I handled the plant roughly or got the juice in a cut or in my mouth, warned me to be careful, and admitted that this was the 'Kombe' or poison plant.
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