The drug continued in use during the middle ages. l'ietro Crescenzio 1 who lived in the 13th century mentions the collection of the seeds in Italy; and Simon Januensis, physician to Pope Nicolas IV. (A.D. 1288-1292), describes them-"propter excellentem operationem in caputpurgio." Description-The fruit consists of three downy follicles, in each of which about 12 seeds are closely packed in two rows. The seeds (which alone are found in commerce) are about 3 lines in length and rather less in width; they have the form of a very irregular 4-sided pyramid, of which one side, much broader than the others, is distinctly vaulted. They are sharp-angled, a little flattened, and very rough, the testa being both wrinkled and deeply pitted. The latter is blackishbrown, dull and earthy-looking, rather brittle, yet not hard. It encloses a soft, whitish, oily albumen with a minute embryo at its sharper end. The seeds have a bitter taste and occasion a tingling sensation when chewed. Ten of them weigh about 6 grains. Microscopic Structure-The epidermis of the seed consists of one layer of large cells, either nearly cubical or longitudinally extended : hence the wrinkles of the surface. The brown walls of these cells are moderately thickened by secondary deposits, which may be made very obvious by macerating thin sections in a solution of chromic acid, 1 p. in 100 p. of water. By this treatment numerous crystals after a short time make their appearance,-without doubt the chromate of one of the alkaloids of staphisagria. The outer layer of the testa is made up of thin-walled narrow cells, which become larger near the edges of the seed and in the superficial wrinkles. They contain a small number of minute starch granules and are not altered on addition of a salt of iron. The interior layer exhibits a single row of small, densely-packed cells. The albumen is composed of the usual tissue loaded with granules of albuminoid matter and drops of fatty oil. Chemical Composition-The analyses of Brandes (1819), and of Lassaigne and Feneulle (1819) have shown this drug to contain a basic principle which has been named Delphinine or Delphine. Erdmann in 1864 assigned it the formula C24H35NO2; he obtained it to the extent of 1 per mille in small rhombohedric crystals fusing at 120° C., soluble in ether, alcohol, chloroform, or benzol. Its salts, except the chromate, appear to be uncrystallizable. The alkaloid has an extremely burning and acrid taste, and is highly poisonous. Couerbe 3 in 1833 pointed out the presence in stavesacre of a second alkaloid separable from delphinine by ether in which it is insoluble. It is called Staphisaïne and has the composition C16H23 NO2. The treatment of the shell of the seed with chromic acid, detailed above, shows that this part of the drug is the principal seat of the alkaloids; and the albumen indeed furnishes no crystals of any chromate. In confirmation of this view we exhausted about 400 grammes of the entire seeds with warm spirit of wine acidulated with a little acetic acid. The liquid was allowed to evaporate and the residue mixed with warm water. The solution thus obtained, separated from the resin, yielded on 1 Libro della Agricultura, Venet. (1511). lib. vi. c. 108. 2 Clavis Sanationis, Venet. 1510. 1 addition of chromic acid an abundant precipitate of chromate of delphinine. The same solution likewise furnished copious precipitates when bichloride of platinum,' iodohydrargyrate of potassium or bichromate of potassium were added. We ascertained that pure acetate of delphinine gives the same reactions with these tests. By repeating the above treatment on a larger scale we obtained crystals of delphinine of considerable size, and also a second alkaloid, not soluble in ether, probably Couerbe's staphisaïne. In 1864, Darbel in a thesis 2 published at Montpellier, announced the existence of a third alkaloid which he termed Staphisagrine--a name which unfortunately has been also applied to staphisaïne. By exhausting stavesacre seeds with boiling ether, we got 27 per cent. of fatty oil, which continued fluid even at -5° C. It concreted by means of hyponitric acid, and is therefore to be reckoned among the non-drying oils. The drug air-dry contains 8 per cent. of hydroscopic water. Dried at 100° C., and incinerated it left 8.7 per cent. of ash. Nothing exact is known of the Delphinic acid of Hofschläger (about 1820) said to be crystalline and volatile. Commerce-The seeds are imported from Trieste and from the south of France, especially from Nismes, near which city as well as in Italy (Puglia) the plant is cultivated. 8 Uses-Stavesacre seeds are still employed as in old times for the destruction of pediculi in the human subject, for which purpose they are reduced to powder which is dusted among the hair. Dr. Balmanno Squire having ascertained that prurigo senilis is dependent on the presence of pediculus, has recommended an ointment of which the essential ingredient is the fatty oil of stavesacre seeds extracted by ether. It is plain that such a preparation would contain delphinine. Delphinine itself has been used externally in neuralgic affections. Stavesacre seeds are largely consumed for destroying the pediculi that infest cattle. RADIX ACONITI. Tuber Aconiti; Aconite Root; F. Racine d'Aconit; G. Eisenhutknollen, Sturmhutknollen. Botanical Origin-Aconitum Napellus L.-This widely-diffused and most variable species grows chiefly in the mountainous districts of the temperate parts of the northern hemisphere. It is of frequent occurrence throughout the chain of the Alps up to more than 6500 feet, the Pyrenees, the mountains of Germany and Austria, and is also found in Denmark and Sweden. It has become naturalized in a few spots in the west of England and in South Wales. Eastward it grows throughout the whole of Siberia, extending to the mountain ranges of the Pacific coast of North America. It occurs in company with other species on the Himalaya at 10,000 to 16,000 feet above the sea-level. The plant is cultivated for medicinal use and also for ornament. The platinic compound is in fine microscopic crystals. Recherches chimiques et physiologiques sur les alcaloides du Delphinium Staphis 3 Pharm. Journ. vi. (1865) 405. 4 We use the word root as most in accordance with the teaching of English botanists. History The 'AKOVITOV of the Greeks and the Aconitum of the Romans are held to refer to the genus under notice, if not precisely to A. Napellus. The ancients were well aware of the poisonous properties of the aconites, though the plants were not more exactly distinguished until the close of the middle ages. Aconite has been widely employed as an arrow-poison. It was used by the ancient Chinese, and is still in requisition among the less civilized of the hill tribes of India. Something of the same kind was in vogue among the aborigines of ancient Gaul.2 One of the most remarkable facts in the history of the species under notice is that in certain localities its poisonous qualities are not developed, and it is so entirely innocuous that it is used as a potherb! This was pointed out as long ago as 1671 by Martin Bernhard,3 an eminent Polish physician and botanist, and was confirmed by Linnæus* so far as relates to Lapland, where the young shoots of one species are cooked and eaten. It is still more strange to find that while in certain districts of Northern India the roots are collected as a poison, there are others in which the same roots are eaten as "a pleasant tonic."5 Störck of Vienna introduced aconite into medical practice about the year 1762,6 Description-The herbaceous annual stem of aconite starts from an elongated conical tuberous root 2 to 4 inches long and sometimes as much as an inch in thickness. This root tapers off in a long tail, while numerous branching rootlets spring from its sides. If dug up in the summer it will be found that a second and younger root (occasionally a third) is attached to it near its summit by a very short branch, and is growing out of it on one side. This second root has a bud at the top which is destined to produce the stem of the next season. It attains its maximum development at the latter part of the year, the parent root meanwhile becoming shrivelled and decayed. This form of growth is therefore analogous to that of an orchis. The dried root is more or less conical or tapering, enlarged and knotty at the summit which is crowned with the base of the stem. It is from 2 to 3 or 4 inches long and at top from to 1 inch thick. The tuberlike portion of the root is more slender, much shrivelled longitudinally, and beset with the prominent bases of rootlets. The drug is of a dark brown; when dry it breaks with a short fracture exhibiting a white and farinaceous, or brownish, or grey inner substance sometimes hollow in the centre. A transverse section of a sound root shows a pure white central portion (pith) which is many-sided and has at each of its projecting angles a thin fibro-vascular bundle. In the fresh state the root of aconite has a sharp odour of radish which disappears on drying. Its taste which is at first sweetish soon becomes alarmingly acrid, accompanied with sensations of tingling and numbness. Microscopic Structure-The tuberous root as seen in a transverse 1 F. Porter Smith, Mat. Med. and Nat. Hist. of China, Shanghai, 1871. 2, 3. 2 Pliny, lib. xxvii. c. 76, also xxv. 25. 3 Napellus in Poloniâ non venenosusEphem. Acad. Nat. Curios. Dec. i. ann. 2 (1671) 79. Flor. Lapponica, ed. 2. 1792. 187. 5 Munro, quoted by Hooker and Thomson, Flor. Ind. i. (1855) 58. 2nd part. 6 De Stramonio, Hyoscyamo et Aconito, Vindob. 1762. section, consists of a central part enclosed by a delicate cambial zone. The outer part of this central portion exhibits a thin brownish layer made up of a single row of cells (kernscheide of the Germans). This is more distinctly obvious in the rootlets, which also show numerous, scattered, thick-walled cells of a yellow colour. The fibro-vascular bundles of aconite root are devoid of true ligneous cells; its tissue is for the largest part built up of uniform parenchymatous cells loaded with starch granules. Chemical Composition - Aconite contains chemical principles which are of great interest on account of their virulent effects on the animal economy. The first to be mentioned is Aconitine, discovered by Geiger and Hesse in 1833, and obtainable from the root to the extent of 3 or 4 per mille. Von Planta (1850) assigned to it the formula C30 H47NO7; Duquesnel1 (1871), whose analysis relates to crystallized aconitine (of A. Napellus) C54H40NO2. For many years it was only known in the form of a light, pulverizable, colourless, amorphous mass. In the London Exhibition of 1862, Morson, the well-known manufacturing chemist, whose aconitine had long been held in great repute, exhibited it in large well-defined crystals. On the same occasion small specimens of the crystallized alkaloid were shown by Groves of Weymouth, and also crystallized hydrochlorate, hydriodate, and nitrate, prepared two years previously by a process he afterwards described in print.2 About the year 1858 it became known to chemists that a substance was being sold under the name of Aconitine, the properties of which were somewhat diverse from those held to be characteristic of that alkaloid, and there was much doubt and speculation as to its origin. It is now known that this body, which is named Pseud-aconitine, and has been also termed English Aconitine, Napelline (Wiggers), Nepaline (Flückiger), and Acraconitine (Ludwig), is derived from the aconite. called in India Bish (see p. 12), which English manufacturing chemists have long preferred (whenever it could be obtained) to the aconite root. of Europe. With these facts in view, and a plentiful supply of each kind of aconite, Groves has re-examined the alkaloids of this drug; and his experiments, though not yet (January 1874) concluded, have established the following facts: European aconite root, derived from A. Napellus, affords aconitine in two forms, crystalline and amorphous. Indian or Nepal aconite root, presumed to be obtained chiefly from A. ferox, yields a closely allied substance, Pseud-aconitine, also under two forms,-crystalline and amorphous. The characters by which these substances are distinguished have been thus recorded by Mr. Groves.3 Aconitine, whether crystalline or amorphous, does not fuse or soften in boiling water. Crystalline Pseud-aconitine does not soften in boiling water, but if 1 Journ. de Pharm. et de Chim. xiv. (1871) 94; De l'Aconitiné cristallisée et des préparations d'aconit, quoted in Pharm. Journ. Jan. 27, 1872. 602. 2 Pharm Journ. viii. (1867) 118.-The crystallized salt shows that the aconitine of Groves was that of A. Napellus. We cannot undertake to say whether the crystallized aconitine of Morson was this alkaloid, or whether it was that now known as Pseud-aconitine. 3 Pharm. Journ. Oct. 11, 1873. 293-296. dissolved in an acid and then precipitated by ammonia, the precipitate treated with boiling water coheres and becomes plastic. Amorphous Pseud-aconitine, boiled in water, fuses, becomes sticky, and adheres to the sides of the vessel. Crystalline Aconitine is far more soluble in weak aqueous ammonia1 than its allied alkaloids. The proportions may be roughly stated thus:cryst. aconitine, 1 part in 500 parts; amorph. aconitine, 1-1000; cryst. pseud-aconitine, 1-2500; amorph. pseud-aconitine, 1-1500. Aconitine and pseud-aconitine are both deposited in crystals from aqueous ammoniacal solutions. Such a solution of crystalline aconitine speedily undergoes spontaneous decomposition; that of amorphous aconitine is more stable, while similar solutions of pseud-aconitine are but little prone to change. Crystalline aconitine forms numerous crystallizable salts: crystalline pseud-aconitine appears incapable of affording crystallizable salts. The crystals of aconitine are described by Groves as being entirely different in form from those of pseud-aconitine. According to Duquesnel those of the former are rhombic or hexagonal tables, sometimes short four-sided prisms. Duquesnel who has studied with attention the proporties of crystalline aconitine obtained from A. Napellus grown in Europe, describes it as anhydrous, nearly insoluble in water even at 100° C. When obtained by precipitation from one of its salts, it is in the form of an amorphous, pulverulent hydrate. The crystals of the alkaloid dissolve in alcohol, ether, acetic ether, benzol, and especially in chloroform which is their best solvent; the solutions have an intensely bitter taste followed by a sensation of pricking and tingling. Crystalline aconitine is freely soluble in dilute acids, easily affording crystallizable salts (especially a nitrate), provided the solution is perfectly neutral; it also forms crystalline compounds with iodine and bromine. Pseud-aconitine is but little soluble in ether (1 in 100), chloroform (1 in 230), or spirit of wine in the cold, but dissolves more freely in those liquids when heated, crystallizing in large prisms from boiling saturated solutions. Solution of pseud-aconitine has a burning but not a bitter taste. In 1857, Hübschmann 2 announced the discovery in the root of A. Napellus of a new base which he called Napelline. It is described as a pulverulent, white, amorphous substance, having a bitter and burning. taste, easily soluble in water, chloroform, or alcohol, but insoluble in ether or benzol. The substance has an alkaline reaction, and is a strong base. Hübschmann subsequently (1867) expressed his belief that napelline was identical with one of the alkaloids he had obtained in 1865 from the root of A. Lycoctonum L.," and had described as Acolyctine. Groves (1873) has prepared a somewhat similar body from Nepal aconite, but has not yet determined its identity or otherwise with Hübschmann's napelline-in fact he has expressed the opinion that European and Indian aconite have each its own napelline. Another alkaloid occurring in aconite was announced in 1864 by T. and H. Smith, of Edinburgh, who named it Aconella, but afterwards 4 1 A solution containing 14 per cent. of ammonia. Flückiger, in Pharm. Journ. Aug. 13, 1870. 121. distinct and well 3 Hübschmann's marked, crystallizable alkaloid Lycoctonine |