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Las diagrammea suivants illustrant la mAthode. 1 2 3 1 2 3 4 5 6 - r.^nT-j :if!T'"V' '.^^vr—'f,^- •?» K? tf AN INAUGURAL DISSERTATION ON STRYCHNIA: PRESENTED TO THE MAY 1st, 1858, PRIOR TO RECEIVING THE DEGREE OF DOCTOR OF MEDICINE AND SURGERY. BY ALEXANDER P. REID. PRINTED BY JOHN LOVBLL, AT THE CANADA DIRECTORY OFFICE flTt RIoaOIiAa STRUT. 1658» ^ ^ ^-r* 7?2T3ii ;_ < * ' _r.^^ '' .W'E AV INAUGURAL DISSERTATION ON STRYCHNIA: PRESKNTBD TO THE tbkal Jfacultg of Pc^ill College, MAY 1st, 1858, PRIOR TO RECEIVING THE DEGREE OF DOCTOR 01 MEDICINE AND SURGKRT. BY ALEXANDER P. REID, IHontital : PRINTED BY JOHN LOVELL, AT THE CANAD.A DIRECTORY OFPICK, 8T. NICKOLAS STREET. 1858. ro TO eiaiUtam WLxiffyt, MM., PBorissoR or matrria ubdioa in moqilii oollioi, AHD TO TBI OTBBB iKembttB of tfie f^UUttal JTacuItg of tfjat QEnbetsttg, TBI rOLLOWINO PAQKS ABB DBDIOATIO. AS A TBIBUTB OF rROSNDJHIP, AMD ALSO OF OBATITCDI FOR THB GREAT BENEFIT DERIVED FROU THEIR VALUABLE TKAOHINO, AND TBB MANY INSTANCES OF PERSONAL KINDNESS, BT THIIB FRIEND AND FORMER PUPIL, THE AUTHOE T theii tatic awai bati( gent its ( liniH supj heh larly give prac in th Med: since purs Irela devo The Medical Faculty ofMcGill College desirous of marking their appreciation of the high merits of the Inaugural Disser- tation on Strychnia, by Alkxandek P. Reid, M.D., have awarded it the unusual dislinctiun of publication. The appro- bation, thus bestowed, iialls upon the production of a young gentleman who had to contend against several difficulties in its composition. Without the aid of superior directions, limited to a few of the treatises in more common use, and un- supplied with chemical auxiliaries of the more delicate sort, he has yet managed to put forth many originalities, particu- larly in the experimental department of Toxicology, and to give them such a maturity of elaboration as fits them for practical employment. His Essay is founded upon one to which, in the previous year, was adjudged the premium in the Materia Medica Class of the University. The leisure the author has since enjoyed, and the opportunities afibrded him while further pursuing his studies in the chief cities of Great Britain and Ireland, have not been allowed to pass away without being devoted to the work of its improvement. CONTENTS. Paoi History, 9 Preparation, 9 Chemical Cliaracteristics and Sensible Properties, 11 Tests 11 Delicacy of Tests, IB Experiments on Animals, 15 Detection in Organic Liquids, 17 Action of Teats with Nux Vomica, 18 Stryciinia obtained from Compound Solutions, 19 Physiological Effects, 19 On Vegetables 19 On Animals, 20 On Man, 20 Post-mortem appearances, 21 Modus operandi 21 Uses, • 23 Administration, 24 Antidotes, 24 Salts of Strychnia, 27 Strychnia with Oxygen acids, 27 Sulphate of Strychnia, 28 Nitrate " 28 Acetate " 28 Strychnate " 28 Tannate " 28 Chromate " 29 Carbazotate " 29 Benzoate " 29 Gallate " 29 Strychnia with Halogen Raaicals, 30 Strychnia and Chlorine, 30 Hydrochlorate of Strychnia, 30 Cbloruretted Hydrochlorate of Stryclmiai 31 VUl. Strychnia and Iodine, 31 Hjdriodatc of Strychnia, 31 loduretted Hydriodate of Strychnia, 31 Strychnia and Bromine, 33 Hydrobromate of Strychnia, 33 Promiurettcd Hydrobromate of Strychnia, 33 Strychnia and Fluorine, 33 Strychnia and Cyanogen 33 Hydrocyanate of Strychnia, 33 Hydroferrocyanatc of Strychnia, 35 Hydrosiilphocyauate of Strychnia, 30 Strychnia with tiie Metals, 36 Metal acting as an Acid — Strychnia and Antimony, 36 Antimoniatc of Strychnia, 3G Strychnia and Arsenic, 36 Arsenite of Strychnia, 36 Arseniate do., 36 The JFetal acting in part as a base with Strychnia — Strychnia and Copper, 31 Double Sulphate of Copper and Strychnia, 3t Strychnia and Platinum, 31 Hydrochlorate of Strychnia and Platinum, 37 Strychnia and Mercury, 38 Hydrochlorate of Strychnia and Mercury, 38 Hydrocyanate do. do., 38 Strychnia and Iron, 38 Hydriodate of Strychnia and Iron, 38 . . 31 . . 31 .. 31 . . 33 .. 33 .. 33 .. 33 . . 33 .. 33 , .. 35 . .. 3G . .. 36 . .. 36 . .. 36 ... 36 ... 36 ... 36 and ... 31 .... 3t .... 37 .... 37 38 38 38 38 ... 38 STEYCHNIA. History. — This r.lkaloid, called also Vauquelina and Tetanine, was ■discovered in 1818 by Pelletier and Caventou. It is found in the Stryclinos Nux Vomica, S Ignatia, S. Colubrina, &c. It is for the most part united with another alkaloidal principle, Brucia, and both are combined with an acid, the Strychnic or Igasuric. It is the active prin- ciple of these plants, and is the agent that causes the fatal effects in death resulting from ingestion of Nux vomica, Ignatius bean, and of false Angustura bark. Brucia is even said to be merely strychnia combined with coloring matter. Pkeparation. — It is chiefly obtained from nux vomica bean. The different Pharmacopoeias give a method for its preparation. The most common plan is to make two decoctions of the coarse powder of the seeds, or digest it in water acidulated with sulphuric acid — the latter is the most preferable — and to this lime is added, which combines with strychnic and sulphuric acids, leaving stryclmia and brucia free. All fall down. The alkaloids are separated from the precipitate by alchohol ; they are again converted into sulphates, and are isolated by ammonia; they are furthermore dissolved in hot alcohol and decolorized, and the solution, upon cooling, deposits the strychnia, while the brucia remains dissolved. Molyn's method is to subject the powder to fermentation with yeast for 10 days, thereby facilitating the subsequent process. This is proposed on account of the mucilage which the seeds contain, causing the decom- position of the saccharic and gummy constituents, evolving carbonic acid, and forming lactic acid, which, acting on the strychnate, forms the soluble lactates of the alkaloids. The seeds generally contain one part of the alkaloid in 200, but the St. Ignatius bean yields 1.4 per cent., according to Christison. 10 I have prepared this alkaloid in a different manner, by adding, to the acidified decoction, iodine dissolved in iodide of potassium. An insoluble compound is thrown down, from which the iodine maybe abstracted by liquor potassae ; this, when decolorized, may be crystallized from its solution in alcohol. In this method the iodine may he all saved, as it can bo easily separated from the filtered solution. Bromine appears to act similarly to iodine in this respect. From analogy, I should think that chlorine might be economically used instead of either of the two substances previously iiiontioned. The great difficulty appears to be its application in the ^^seous condition. I have found, however, that by treating the acid decoction with chloride (hypochlorite) of soda, (made by precipitation from hypochlorite of lime and carbonate of soda) which, when washed and dried, is to be acted on by liq. potass,, although liq. soda would answer the same pnrpose, the precipitate appears to difsolve when the alkali is added, but the strychnia falls to the bottom in flocculent masses. It should be collected and decolorized in the usual manner, and then crystallized from alcohol, or from solution of a sulphate as a salt. In these processes I prefer the hypochlorite of soda formed by preci- pitating the lime from the solution of the hypochlorite by carbonate of soda. This preparation is far superior to the common article, in being much purer, because when chlorine gas is conductel into solution of carbonate of soda only half of the base unites with the chlorine, the other existing as bicarbonate of the alkali, and thus is rendered so far impure ; and in general it is a much weaker compound, on account of the diffi- culty in causing the chlorine to be absorbed, which is not the case with' lime in the form of caustic hydrate. I find it almost impossible to pre- cipitate strychnia in the acidified decoction by the common preparation, although readily affected by the other solution. While engaged with these preparations, I was led to believe that the chemical constitution of hypochlorite of soda i'^ different from that gene- rally received and that in reality it is a chloruretted chloride of sodium, or a solution of chlorine in chloride of sodium, with other compounds of these elements existing as impurities from faulty manufacture, thus resembling tho ioduretted iodide of potassium. When chlorine is con- ducted into a ilution of soda, chloride of sodium and chlorate of soda are first formed, and then free chloiinc remains in the liquid, llypochlo- rous acid is also formed, and appears to be due to the action of chlorine on chlorate of the alkali, and not, as has been said, to the union of its oxygen with the haloid radical directly, because combination does not occur unless the elements have been some time acting on one another, 11 iove that the and upon the addition of an acid, as the sulphuric, chlorine gas, almost pure, is evolved. Sensiule Properties. — When pure, strychnia is a crystalline sub- stance — white, inodorous, and intensely bitter ; when rapidly crystallized it is granular, but by the spontaneous evaporation of the alcoholic solution it takes the form of the octohffidron or four-sided prism. It is fusible, but not volatile. The bitterness is such, that 1 part is distinguishable in 80.000 of water. Chemical Characters. — Equivalent weight, 334. Composition, C42H22>^2 0* (Rcgnault), C30II16NO3 (Liebig). It is very insoluble in water, requiring G667 parts for complete solution at 50° F., equnl to about 14 ounces of water for each grain ; of boiling water it requires 2200 parts. It is almost insoluble in absolute alcohol or ether when in its free state, but more soluble in common alcohol; by heating, this pro- perty is still farther increased. It is also moderately soluble in fixed and volatile oils. As an alkaloid it saturates acids, and even displaces other vegetable bases, as brucia and morphia, and also some metallic oxides are partly separated from tlieir combinations with acids forming double salts. It is destroyed by a heat under that of redness. Sulphuretted hydrogen is evolved when it is fused with sulphur. It is very soluble in diluted acids, forming salts. The common strychnia is reddened by nitric acid, but if pure is unaffected : the color is due to the action of the acid on brucia. Tests. — 1st.* It is found crystallized in short prisms, or as a greyish powder with a bitter taste. 2nd. Scarcely soluble in alcohol and water, and slightly so in ether, but readily in acetic acid. «3rd. Heated on platinum foil it burns, becomes charred, evolving a smoky flame and poisonous vapour, leaving a residue of carbon. 4th. Nitric acid reddens it, without evolving nitrous acid. 5th. Soluble in diluted acids, and from a hot solution crystals may be deposited on cooling, 6tli. The solution is precipitated by tannic acid or tincture of galls. Vth. Alkalies, as ammonia, give a white precipitate. 8th. It is precipitated yellowish- white by terchloride of gold, whereas morphia reduces gold. The precipitate with gold is not re-dissolved by boiling, but the liquid acquires a pink-rod color, and on the other hand morphia gives the metallic gold in powder. 9th. The red color by nitric acid is discharged by chloride of tin. 10th. It is unaffected by sosquichloride of iron or iodic acid and starch ; it is thus also distinguished from morphia, llth. Potash pre- cipitates the alkaloid from its salt, and it is not easily re-di?solved by * These tests are taken from Taylor's " Medical Jurisprudence." 18 excess of precipitant?, whereas morphia is only precipitated from a strong solution, and it is easily dissolved by slight excess of potassa. 12th. Strong sulphuric acid produces no change of colour in pure strychnia, but if a drop of solution of bichromate of potash be added, the mixture acquires a crimson hue, passing to deep blood-red; or if, instead of the bichromate, either the the deutoxides of manganese or lead be added, a very nice play of colors is produced, which passes through shades of blue, violet, purple, and crimson, to blood-red. I do not think that the bichromate answers as well as either of the others, because the acid causes a colour with it much like what strychnia produces, and in weak solutions this might be a fallacy that is not liable to be met when the others are used. Morphia causes a green-tinted fluid with these testa. 13th. White tinted precipitates are caused by iodide of potassium, and the sulphocyanide of this same base gives white crystals. Solution of bichloride of platinum gives a yellow powder. There is a newer test than these, the aqtive agent of which is elec- tricity. When the two poles of a powerful battery are brought in contact in the fluid containing strychnia, placed within a depression on a piece of platinum foil, a series of colours are produced. In reality we have no good test for strychnia in solution upon which we can rely in difficulty. This was clearly evident in the trial of Palmer for poisoning Cooke by strychnia, where the presence of this alkaloid could not be proved. Nevertheless strychnia is a substance which has really marked and peculiar chemical qualities : it is a base easily separated from the com- bination in nux vomica, and by no means hypothetical, like methyl, acetyl, etc. Remembering these facts, and that it forms distinct com- pounds with numerous and varied elements, that through them, it may be separated from complex mixtun^s, whether mechanical or even che- mical, and that it gives distinctive reactions with various agents at the command of the practical chemist, either as regards colour or precipitate, or both, I commenced a few investigations with regard to its chemical properties, to find if it would not be possible to detect small quantities, and be able to separate it from organic mixtures, by some newer and more certain method than those in vogue. As far as I am able to judge, I have found out a method by which I can accomplish these ends, and likewise detect some of the other alkaloids. It is a very simple one, and I trust will be found useful. I found that by a certain re-agent with which I was manipulating, a deep brick-red or brown- coloured precipitate was thrown down from a solution of strychnia, but caused no change with the mineral acids, sulphuric, nitric, hydrochloric, 13 from a strong )tas3a. 12t,h. ire strychnia, 1, the mixture nstead of the i be added, a gh shades of hink that the ause the acid 1, and in weak met when the h these tests. )otassinm, and . Sohition of wliich is elec- re brought in , depression on on upon which trial of Pahner f this alkaloid ly marked and from the com- 1, like methyl, s distinct com- 1 them, it may al or even che- various agents ards colour or with regard to isible to detect ic mixtures, by JO. As far as I can accomplish s. It is a very lat by a certain red or brown- strychnia, but c, hydrochloric, or phosphoric, nor none with the acetic, oxalic, or hydrocyanic. No similar effect was produced in any luetallic solution or compound, and I tried all tlie comm.on bases, alkaline and mineral, nor in a solution of sugar or dextrine. The alkaloidal ]>recipitate is deposited in all acid solutions (except that of the nitric if strong). It is decomposed when boiled with the other strong mineral acids. The only objections are, that quinine and veratrine give somewhat similar precipitates, but morphia produces no visible change. The veratria precipitate may appear similar at first, but becomes of a light yellow colour when washed and dried. That with quinine is very dark brown ; whereas that with strychnia is a tint between the other two, or brick-red. Bebeerine causesi a precipitate very similar to quinine and very difficult to distinguish from it. Santouine gives no apparent re-action. The strychnia precipitate is easily distinguished by compari- son with the others, and more surely by a method to be mentioned in another place. The re-agent used, nnd above referred to, was the saturated solution of iodine in a solution of iodide of potassium, diluted so as to present a cherry-red tint. The iodine will not act in the compound state, or I should rather say as an iodide, because it then gives another kind of precipitate, the iodide of strychnia, which is a white crystalline salt. The ioduretted solution is to be added drop by drop to the strychnia. As each one arrives at the bottom of the test-tube, it appears tp be fringed by a dirly-white precipitate, which when agitated, acquires a brownish colour. Upon standing, a sediment of the same tint subsides from this mixture ; unless in a very dilute solution, when it remains suspended, causing a muddy appearance. This differs materially from the effect it causes with water ; then, only, the drop falls to the bottom, without even tinging the fluid, and when shaken up, gives a transparent solution of the peculiar iodine tinge ; no further change resulting as the iodine is soluble in the iodide of potassium which is present. If the re-agent be added to a strychnia solution, in which blood exists, the colour of the precipitate is masked ; but, if much of the alkaloid be present, it can be easily distinguished, and if allowed to stand, will fall to the bottom, and, upon being collected, its nature can be det-^rmined. The bitter infusions give no re-action with the test, and iu theui strych- nia can be detected without any difficulty. If the stiychnia precipitate be acted on by strong sul[)huric acid, it becomes brownish- yellow. That with veratria, gives with the same acid, a beautiful play of colours, first yellow, next red, and then violet. Quina and bebeerina similarly acted on become greyish-brown. 14 Strong nitric acid produces nothing characteristic with cither, and there is the same absence of distinguishing change when sulphuric acid and bichromate of potash are used. But, if in place of the last-mentioned salt, binoxide of manganese be used, the strychnia precipitate becomes first purple inclining to red, then reddish-brown ; at other times a greater play of colours is elicited, but with veratria, bebeerina and quina nothing remarkable is visible. Another test previously mentioned, as applied to the solid substance, which I have found yielding valuable information, is sulphuric acid and a Solution of bichromate of potash added to a very dilute solution of strychnia. I prepare this test by adding to an ounce of water as much of H saturated solution of the salt just named as will render the whole of a light straw-yellow colour, say about 16 drops, and then about 50 drops of the acid. To a part of this mixture the liquid, containing strychnia* is to be added and then boiled ; at first there is no change, but as the fluid becomes hotter, the colour becomes gradually deeper in tint and finally blood-red. If the desired alteration be not brought about, it may be hastened by a few drops of sulphuric acid. If the solution of strych- nia be very dilute, it will be better to add the proper amount of acid and salt directly to it and then proceed as in the former case ; but sometimes the fluid will require to be boiled for a good while, even several minutes, before any change biicomes visible, and sometimes it will not form until it cools, but then it is not generally well marked. It may be said that sulphuric acid will cause this change by acting on the solution of bichromate, even when no strychnia is present. To effect this, however, both agents must exist in very large quantity, and even then the colour differs much, being lighter and inclining to a rose tint ; but if it be merely of the strength mentioned tliere is no visible change even after prolonged ebullition. This test it will be observed differs fi'ora the same ap lication of the same re-agent to solid strychnia in several j.'oints, as in the requirement of heat, &c. ; and of the two it is the most delicate. I have not yet found any substance that will give the same result with this mixture that strychnia does. It is bleached by morphia and after a time the groen oxide of chrome is precipitated. Veratria causes no change nor does quina. Neither blood, sugar, starch, nor dextrine give any ajipearanees that constitute an objection. Iodine, sugar, and most organic liquids dissipate the colour of the t^olution. Chloride of lime has the . anio effect. Santonine, bcbeerine, too alkalies, acids, and all others I have tried appear to be equally negative. If the iodine test be added to the bichromate test, when reddened by 16 th either, and sulphuric acid last-mentioned pitate becomes other times a jrina and quina lolid substance, huric acid and ute solution of water as much er the whole of about 60 drops ining strychnia* ngc, but as the per in tint and lit about, it may lution of strych- )unt of acid and but sometimes I, even several ;imes it will not ked. ige by acting on esent. To effect antity, and even g to a rose tint ; visible (•hanfje rvcd differs from [•linia in several ,vo it is the most same result with orphia and after eratria causes no or dextrine give sugar, and most Chloride of lime s, acids, and all hen reddened by strychnia, a dense reddish brown precipitate falls, but if added to one containing no strychnia a dark green is founed. Liebig mentions that if chlorine be added m a solution of this alka- loid it causes a white precipitate and that bromine acts similarly. I have found that a watery solution of bromine gives a yellowish tinted precipitate with strychnia, but it is not more than one fourth as delicate as that of iodine, resulting probalily from the light colour which is given by it in contradistinction to the brown afforded by the ioduietted solu- tion, neither is there the same opacity of the mixture produced with the former as with the latter I have not found that solution of chlorine gas gives nearly so well marked a re-action as that of the chlorurelted solu- tion before mentioned. It might have the advantage of decolorizing or- ganic liquid, but as a t.'st is not at all desirable. Delicacy of Tests. — With the ioduretted solution I can detect one grain in solution in four pints of ordinary water, and in pure water by comparison I can discover the presence of one grain in a gallon of the fluid. In this case the liquid becomes milky from the precipitate being suspended in it, and it is so light that it will scarcely fall to the bottom, and if we allow that the ounce of water weighs 500 grains, then one part o^ btrychnia can be thus detected in 64,000 of water nearly. I have even been sensible of its presence in solutions much weaker than these. With the bichromate solution test I find it is difficult to distinguish one part in 16,000 of water. This test is most distinctive and can be relied on if the proper change appears, hut this will not be brou(>ht about if any organic, compound l)e present at the lime ; even the presence of a little alcohol being enough to mask that of the alkaloid. Experiments ON Animals. — I poisoned a chicken with the cyanide of strychnia. At first I gave it the g-'j-th of a graii> and in two hours g'jlh more; in twenty-four hours it got -j-Lth of a grain, and in twenty-four hours or thereabouts, after it had recovered from the previous effects, I gave it the ^th of a grain, which caused death. I then separately boiled in water, acidulated with sulphuric, acirl, the contents of the crop, the Tuembrano itself, the intestines, the liver, the lungs, the brain, and the spinal cord. After removing any great excess of the acid by carbonate of lime I tried all the tests for the alkaloid, but failed in getting any re- liable result.. The bichromate solution was decoh)iized, and the iodine test gave the appearances to be mentioned in a subsequent page, which rendered it im[)ossil)le to be certain ot the i>iodm t, the liquids being very high coloured. Tincture of galls gave a [jrccipitate, but that was caused by the gelatine present. The solutions were then evaporated until almost dry, and this extract 16 r digested in strong alcohol for some days. This solution was evaporated also until most of the alcohol had disappeared ; to this water was added, which dissolved the salt of strycshnia in solution, but threw down sumo white matter insoluble in that fluid. To the filtered products those tents were applied. (1). The ioduretted solution. It caused the characteristic pri-cipitate which was proved to be strychnia by sulphuric acid and binoxide of manganese, or Marchand's test, so that no room could be left for doubt*. Another portion of this, by a method to bo mentioned, yielded the alka- li jiial strychnia and was recognised to be such by the tests given fkom Taylor. (2), The bichromate test. This gave nothing decided, perhaps from a small quantity of urgauic matter being present, which threw down the green oxide of chrome. In adding to tliis the iodine test the strychnia was separated as easily as though it had been a simple solution. (3). The taste tvas found to be bitter. (4). An alkali (potash) did not cause any appreciable precipitate. (5). Tannic acid produced a white curdy precipitate which on re-solution by sulphuric acid was proved to bo strychnia. The evidence of the pre- •enceofthe alkaloid in the liver was well marked, and also in the intes- tines, but not to the same extent. But the largest quantity was found in the crop, as might be supposed.' This part contained rather a homo- geneous mixture, and was (juile filled. The diluted acid extract was a tenacious, gummy mass, of a dark colour. The others were much simi- lar. I also examined the lungs, brain, and spinal cord — each separately — but was not able to detect tlio pre:*ence of the pi>ison. I afterwards examined the stomach of a kitten ])oisoned by j'^jth of a grain of the acetate. It contained bread, meat, and coagulated milk ; upon these being similarly treated, as in the first experiment, a thick muddy liquid was separated. To this mixed solution the iodine test was added, and I thought I could detect the peculiar fringed border when first added,, but on shaking it up there was nothing distinguisiiable other than what is seen in most oruanie mixture^. To this liquor potass, was added, which had no other eflecttlian decolorizing tiic mixture and decomposing the strychnia compound. In a little while the alkaloid fell down as usual, and was proved to be such by Marchand's test, thus doing away with the trouble of evaporating the solution and then again dissolving. The precipitate wa^^ also proved by the bichromate s'dution test. Another kitten was poisoned by the doul)le chloride of mercury and strychnia. The quantity given I do not think could have exceeded 17 ^th of a grain. Tho contonts of the stomach wcro treated as in the former. The iodine test was added to a small quantity of the filtered prodiictp, which caused a change similar to that hist described. When tho potassa was added all tlio precipitate disappeared. To render tho mixture more liquid, water was added. Nothing was seen for some hours, but gradually a very light flocculent precipitate appeared and gradually sank to tho bottom. This was proved to be the alkaloid by Marchand's and tho bichromate test. When a precipitate forms after the addition of potassa it appears to be almost distinctive of strychnia. From tho liver of an animal, poisoned with about the same amount of the same salt, several hours after it had been taken, when treated in a manner similar io tho others, evidence of the presence of the alkaloid was also procured although I only used about the ^'g-th part of tho filtered product. This precipitate was washed three or four times and the play of colours with Marchand's test was very delicate, but yet distinctive. Evidence was also afibrded with the bichromate tost which became visi- bly reddened. When instead of the precipitate I used the filtered liquid this solution was decolorized. I should think, judging from these few experiments, strychnia can be detected in very minute quantities well, when existing in heterogeneous mixtures and in complicated chemical compounds. In the first case mentioned, two Weeks elapsed between the death of the animal and the detection of the poison. Strychnia is not easily decomposed at common temperatures. It has even been found in the urine, and in some cases I have boiled the organic mixtures containing it for very many hours without affecting it. Detection of Strtciinia in Organic Liquids. — The method of procedure in this case is similar in design to that pursued with most other poisons. By boiling the stomach and contents, or any of the vis- cera, as the liver in water, acidified by sulphuric acid, a liquid may be obtained from which the alkaloid may bo separated by evaporation con- ducted almost to dryness, and then acting on it with alcohol which will dissolve the salt of strychnia. If now the alcohol be driven otf, *..'.>. ''^- kaloid will be left almost pure, as detailed in one of the cases 1' i . ' ,it section. The action of these liquids on tho iodine test does not in general vary very much. When first added it appears to separate in flakes, the iodide of gelatine, as if coagulated, and the rest of tho fluid is tinged with it; and in a little while there is a precipitate which sometimes very much resembles that with the alkaloid ; but when it is not present, liq. potass dissolves them all and decolorizes the fluid, although sometimes heat is u I .-■ 18 required to effect tins object, and oven if any wore to remain it would not give ♦ho distinctive re-action with Man-hand's test. If the iodine tost be adL a warm solution of gelatine a ro-action similar to that with stryci appears; but this is no objection, bocauso whoii it is boiled it bcconics liquid, and again on cooling gelatinizes ; and if potassa be added to it, it is readily dissolved and decolorized. The bicliromate solution test is almost invariably decolorized by or- ganic liquids. The iodino t'-st will not act if the strychnia bo in solution in al- cohol, be H' 0^.) This is a soluble salt, and is merely worth mentioning, because this acid does not form an insoluble compound with the base like Tannic Acid, and would serve as a means of distinguishing these two acids. Gallic acid might be a negative proof of Strychnia from this property, which few other elements possess. When the aqueous solution is evaporated, the salt is deposited in colourless scales: these ajjpear in the field of the microscope like thin broken glass fragments. I could not distinguish any distinct crystalline form. It is more soluble than the Benzoate, and is prepared by dissolving the alkaloid in Gallic Acid and evaporat- ing until it takes its peculiar form. It is not very soluble in cold water. One thing a little remarkable about the salt is, that both Strychnia and Gallic Acid are very insoluble in water taken separately ; but when X\ 30 boiled together they foim a very soluble salt, although they will not unite in cold water. Its uses are most likely similar to those of the al- kaloidal base. There are other salts with the Oxygen acids, which have nothing very remarkable about their composition and which are soluble. They are the Lactate, Citrate, Tartrate, Oxalate, Borate and Phosphate. They are all easily prepared by dissolving the alkaloid in each acid res- pectively and evaporating the watery solution. 2. Strychnia with tiik Hai^gen Radicals. — The halogen elements do not unite with the oxide of a -netal or alkali ; and, reasoning from the same premises, we might say that each of the alkaloids is the oxide of some base with which we are unacquainted in its free state ; and it might be supposed, that, when the haloid radical separates from it, oxy- gen immediately combines with it, forming the common alkaloid. This theory would do very well with most of the alkaloids; but there would be a diflSculty with those which do not contain any oxygen at all, and yet unite with the oxygen and hydrogen acids indiscriminately, as Narcotina, and, according to Artigosa, Conia, although Liebig gives to it one equivalent of oxygen ; while LOwig says it does not contain oxy- gen, and that it is decomposed by Chlorine, Iodine, and Bromine, when brought in contact with them. Upon any other view we must suppose alkaloids are peculiarly constituted bodies, in which the elements of combination unite in opposition to ouc generally received laws ; that the same elements hold inviolate with regard to every other substance, not excepting the alkaloids of the alcohol series, except when they unite with an oxygen acid of these compounds, as the chloric. If, on the other hand, we consider these vegetable bases to be elementary with regard to the halogen, then the oxygen acids must forego their usual law and unite with an unoxygenised base, which they do not do with others. Perhaps the halogen radicals, in combining with these bases, displace an equivalent of hydrogen, as they are known to do in the al- cohol series, and also as shown in the formation of the chloride of car- bon, thus acting by substitution. However this may be, I am not in- clined to think that the chemical laws are at all interfered with in these combinations, although the rationale is unexplained; and, in our present state of knowledge on this point, it would be preferable to describe them as if they were bases of oxygen acids ; and, instead of terming them Chlorides, I shall call them Hydrochlorates, and in the same manner as with otber elements. + Strychnia and Chlorine — Hydrochlorate of Strychnia. — St HCl or (C* 3 H2 2 Na 04) HCl.— This salt is officinal in the Dublin Phar- mac Aci( tion in tl equi will as t » macopoea for 1860. It is prepared by disaolving Strychnia in Muriatic Acid. It is deposited in fine crystals as the concentrated boiling solu- tion cools. They are four-sided noodles, which lose their transparency in the air, and when heated give oflllydrochloric Acid. It contains two equivalents of water, and is more soluble than the sulphate. Its uses will be similar to those of pure Strychnine. CiiLORURKTTKD Chloridk OF Stryohnia. — This is formed when a solu- tion of chloride of soda, obtained by precipitating the lime from the commercial chloride of that earth, is added to a solution containing Strychnia. It is a white, insoluble precipitate, and is not crystallizable ; it is, however, very poisonous. Strychnia will most likely form salts with the oxygen acids of chlorine, as the hypochlorous, chlorous, chloric, and perchloric acids. Chlorine, according to Lowig, converts Strychnia into a base contain- ing chlorine, the atoms of hydrogen being replaced by it. He also says thai if this haloid element be added to a soluble salt of the alkaloid it causes a white precipitate. This is most hkely a similar compound with that formed by chloride of soda, before mentioned. Silliman, also, states that both Strychnia and Brucia yield products in which the hydrogen is in part replaced by chlorine. + Strychnia and Iodine — Uydriodate of Strychnia. — St H I or (C*a Haa N" 0*)HI. — This salt is mentioned by LOwig as being in- soluble in water ; but he does not describe any other Iodine co.;)pound but this. Lewuer also states that a soluble salt of this alkaloid is preci- pitated white by Iodide of Potassium. Brande states that if Strychnia be boiled in Iodine and water that it is dissolved. The salt is easily formed by precipitation from Sulphate of Strychnia by Iodide of Potassium. It falls down as a white crystalline powder, which consists of needle-like, irregularly-rounded crystals, and diflfers from most of the others in not being distinctly cubical. It is not soluble, except in a very great quantity of water, and hence must not be washed too freely in preparation. It does not dissolve in Ammonia, nor in Hy- drochloric or Citric Acids, but does in Acetic Acid. Sulphuric and Nitric acids do not act very readily on it if they be dilute ; but, when concentrated, the salt is decomposed and Iodine given olF. It is freely soluble in alcohol. Its uses will most likely be similar to those of the alkaloid itself. The trivial quantity of Iodine which it contains will have little if any influence when united in small quantities with such a powerful base. - '>' loDURETTBD HyDEIODATB OF SlRYCUNIA. — St I, I (C^^ U."" N^ 0*J, 1^ 3a I, I. — This 'compound is the precipitate which falls when the Iodine test is added to a solution of Strychnia. It is not a mere mechanical combination ; because, if so, it would not bo formed under so many ad- verse circumstances ; and, as the Iodine test is the loduretted Iodide of Potassium, I have thought that the alkaloidal combination was similar. The Iodide of Potassium is a colourless salt, and so is the Iodide of Strychnia : for these reasons I have given this precipitate the above- mentioned name. It is easily precipitated from solutions rendered very acid by Sulphuric, Nitric or Acetic acids ; also from solutions contain- ing most metallic salts, and even from organic mixtures. When well washed and dried, it is of a reddish colour, and when deposited from the alcoholic solution by spontaneous evaporation, it appears like cubical blocks of a yellow colour when examined by the microscope, but it is not very distinct ; generally, it is amorphous. The precipitate is light and bulky, comparatively, and is insoluble in water to any great extent; hence its use as a test. It has a slightly bitter taste. When exposed to heat. Iodine fumes are given oflF, leaving a dark-colored residue ; and, if the heat be increased, disagreeable fumes are given off, and a spongy, charred mass is left, even when heated to redness. It is soluble in alco- hol. Diluted Sulphuric, Acetic, Citric and Hydrochloric acids, form mixtures of a light yellow colour, but it is not dissolved. The strong acids decompose it, giving off violet fumes of Iodine. Ammonia and Liq. Potassse abstract the Iodine and leave the Strychnia free as a yellow- ish powder. The uses will most probably be similar to those of the alka- loid ; but, on account of its very great insolubility, its action would not be considered so violent ; but this is doubtful. I gave to a kitten about one-third of a grain, wrapt up in a piece of meat. It caused a great flow of saliva ; resulting, I suppose, from the taste. In twenty minutes pow- erful contractions were caused, but they were scarcely so frequent as when the free alkaloid was given. The respirations became very fre- quent ; but the heart's action was not much increased when compared with that of another kitten of about the same age. The pupils were widely dilated — the irides scarcely to be seen. The veins were all en- gorged with blood, but the lungs not so to a very great extent. The sto- mach was found filled with air. The poisonous particles were found lying around the cardiac orifice, very few being at any other part. I think half the amount taken would have caused death, because a very large portion was still rolled up in the bolus with which it was given. Death was caused in forty minutes. Its inferioritj in point of poisonous effects are, I think, little, if any, inferior to the free alkaloid. The sto- machic mucous membrane did not appear to be the least inflamed where 88 the powder was in contact with it. It app^iared to act independently )f absorption. + Strychnia and BaoMiNS — HYDionROMATK of Strychnia. — St HBor(C«2H"NaO«)HB.— I can find ii.. mention made of this salt in the works to which I have access. It can bo prepared by precipitat- ing a solution of any salt of Strychnia by the Bromide of Potassium. It is a pretty white salt, which ciystallizcs in handles resembling hairs. They aio very long and round. It, like the Iodide, is soluble to a slight extent in water ; am is so, likewise, in diluted acids. Its uses will, moSt likely, bo similar to tiiose of the alkaloid. LOwig and Silliman say that both Strychnia and Brucia can be converted into bases in which the hydro- gen is replaced by Bromine ; being, in this respect, similar to chlorine. Bromiuretted Hydrodromatk op Strychnia. — This is prepared by adding a watery solution of Bromine to a solution of a salt of Strychnia. It is of a yellowish red colour. Its uses will be similar to those of the alkaloid. I gave a kitten ^th of a grain, which caused sickness for a few hours, but no spasms ; but, on this amount being repeated, it proved fatal in about twelve or fifteen minuter, with the usual symptoms. Strychnia and Fluorine. — The Hydrofluorate, although not as yet mentioned by any author, I think could be prepared as most of the homologous compounds are ; but I had not the means of examining it. Strychnia and Cyanookn. — The reactions of Cyanogen, although not an elementary body, approach so closely to those of the haloid group, and bear in reality as much relation to them as Acetic, Citric, Tartaric and other vegetable acids to the miner d oxygen acids, — that I think it can with justice be called the organic halogen radical ; because in all its combinations it reacts similarly, being only decomposed by great heat or exposure to the air, under certain conditions. Hydrocyanate of Strychnia. — St IlCy or (C*^ H" N^ 0*) (II Ca N). — This is a beautiful crystalline salt. Kane says the needles are decomposed by a gentle heat. It is prepared, according to him, by dissolving Strychnia in Hydrocyanic acid ; but, as the salt is insoluble in five per cent acid, the mixture docs not appear to change, and it is difficult to say when the product is obtained. I think that it is very much better to prepare it by precipitation from a solution of Strychnia by Cyanide of Potassium. The temperature of the solution causes a dif- ference in the appearance. If both solutions be cold, it falls as an amor- phous or obscurely crystalline precipitate : under the microscope, it ap- pears like very small needles. If, however, the sulphate of Strychnia M it Holution be at thu boiling point, the pro