Part 22

_Physiological action._ The alkaloids generally possess great medicinal power; some of them act with terrific energy, and are the most violent poisons with which we are acquainted. Perfectly pure aconitia is about 200 times more poisonous than arsenic, and at least 50 times more poisonous than ordinary medicinal prussic acid. The greater number act on animals in the same way as the plants which produce them, provided they are given in proportionately small doses. Many of them, when judiciously administered, are most valuable medicines.

_Pois., Ant., &c._ Some of the alkaloids act as narcotic or stupefying poisons; others are classed with the narcotico-acrid poisons, or those which produce both narcotism and irritation of the parts they touch. The general symptoms produced by opium and its preparations may be taken as an example of the former; those from aconite and strychnia, of the latter. In large doses of the greater number, narcotism predominates; in smaller ones, irritation; they are rarely coexistent.--_Treatm._ No common antidote to the effects of this class of substances has yet been discovered. The only safe treatment, of at all general application, is to immediately clear the stomach by means of a strong and quick-acting emetic (as sulphate of zinc), or the stomach-pump, and to administer copious and continued draughts of astringent vegetable solutions (as of tannin, nut-galls, oak-bark, or what is always at hand--very strong tea or coffee). These may be followed by or combined with a smart purge of castor oil, as soon as the stomach is thoroughly cleared of the poison. M. Bouchardat strongly recommends a solution of iodine, 3 gr., and iodide of potassium, 6 gr., in pure water, 16 fl. oz., in cases of poisoning by OPIUM, ACONITE, COLCHICUM, DEADLY NIGHTSHADE, HEMLOCK, NUX VOMICA, &c., or by the alkaloids obtained from them--ACONITINE, ATROPIA, COLCHICINA, CONIA, MORPHIA, STRYCHNIA, &c., or their salts; but _not_ where foxglove or digitalin has been taken. The stomach having been well emptied by an emetic, the solution is to be given by wine-glassfuls for some time; the vomiting being still encouraged during the early part of the administration of the antidote. In the case of narcotics (as opium, morphia, &c.), this is to be followed by the free use of a strong infusion of coffee. According to Dr Garrod, purified animal charcoal is an 'excellent antidote' to many of the alkaloids, including those above enumerated, when taken in poisonous doses; as it not merely absorbs them, but, for the most part, renders them inert. To be serviceable it should be recently prepared and fresh-burnt; and should be given in doses of about an ounce at a time, diffused in warm or tepid water, and frequently repeated. The vomiting which follows its use, owing to the warm water, proves advantageous; but after a sufficient time may be lessened by employing less water, or cooler or even cold water. Drowsiness, if present, may be combated by the subsequent use of strong coffee or tea, as before. We have seen this plan succeed in several cases.--_Lesions._ These, like the symptoms, vary. In some cases there are redness and inflammation of the stomach and intestines, and turgescence of the vessels of the lungs and brain; in others, these appearances are either slight or wholly wanting. Wherever there has been much cerebral disturbance, traces of congestion are usually discernible.

_Detec., Tests, &c._ The identification of the pure alkaloids is extremely simple; but their detection, when combined with organic and colouring matters, is a task of considerable difficulty. One or other of the following plans may be adopted for this purpose:--

1. (Merck.) The matter under examination is digested, for several hours, with concentrated acetic acid, added in sufficient quantity to produce a strongly acid reaction; the fluid portion is then strained from the insoluble matter, and the latter being washed with water acidulated with acetic acid, the mixed liquors are gently evaporated to dryness in a water bath; the residuum of the evaporation is boiled first with rectified spirit, and next with rectified spirit acidulated with acetic acid; the mixed liquors are again evaporated, the residuum redissolved or diluted with distilled water, and carbonate of soda or potassa added to feebly alkaline reaction, and the whole, after evaporation to the consistence of a syrup, set aside to repose for 24 hours; it is now again diluted with water, filtered, and the insoluble portion washed with cold distilled water, and digested with concentrated acetic acid; this last solution is diluted with distilled water, and decoloured with pure blood-charcoal (if it be necessary); the fluid, either at once, or after cautious evaporation, may then be tested for the alkaloids, in the usual manner. The charcoal previously used should also be tested in the way described below. This method answers admirably with all the NON-VOLATILE ALKALOIDS, and may be applied to the stomach and viscera, and their contents, and to food, &c., in cases of poisoning.

2. (Stas.) The suspected matter, in a finely divided state, is digested, at 160° to 165° Fahr., with twice or thrice its weight of strong alcohol acidulated (according to the quantity) with 1/2 dr. to 2 or 3 dr., or more, of pure oxalic or tartaric acid. After a sufficient time, and when the whole has become quite cold, it is thrown on a filter, and the undissolved portion, after being squeezed dry, is washed with strong alcohol. The mixed and filtered alcoholic liquids are then evaporated at a temperature not exceeding 95° Fahr., and, if no insoluble matter separates, the evaporation is continued nearly to dryness;[19] but if fatty or other insoluble matter separates during the process of concentration, the concentrated fluid is passed through a moistened filter, and the filtrate evaporated nearly to dryness, as before. The residuum is next digested with absolute alcohol, in the cold, the insoluble portion, after filtration, washed with alcohol, and the mixed filtrates again evaporated in the air, or in vacuo. The acid residue is now dissolved in a little distilled water, and bicarbonate of soda added as long as effervescence ensues. To this mixture 4 or 5 times its volume of ether is added, and after lengthened agitation (the bottle or tube being held in a cold wet cloth), the whole is allowed to repose for a short time. A little of the supernatant ether is now removed to a small glass capsule or watch-glass, and allowed to evaporate spontaneously.[19] When this leaves oily streaks upon the glass, which gradually collect into a small drop, which emits, when gently heated, a disagreeable, pungent, and stifling odour, the presence of a LIQUID VOLATILE BASE or ALKALOID is inferred; whilst a solid residue or a turbid fluid with small solid particles floating in it, indicates a NON-VOLATILE SOLID BASE.[20] In either case the blue colour of reddened litmus is permanently restored by the residuum. If no residuum is left on the capsule, some solution of pure soda or potassa is added to the liquid, the whole well agitated for several minutes, and the ether (after repose) decanted; an operation which is repeated with fresh ether a second, third, and even a fourth time. The base, or bases (if any are present), will now be found in the mixed ethereal solution, which is, therefore, tested as before. The presence of an alkaloid being detected, the mixed ethereal solutions are allowed to evaporate spontaneously, care being taken, if a volatile alkaloid be present, to neutralise the liquid with an acid before the final evaporation. The last residuum is then tested for the particular alkaloid present, as before.[21]

[Footnote 19: The evaporation, according to Stas, should be conducted under a bell-glass over sulphuric acid, with or without rarefaction of the air; or in a tubular retort through which a current of air is made to pass.]

[Footnote 20: A merely disagreeable animal odour, without pungency, is here disregarded.]

[Footnote 21: 'Bulletin de l'Académie de Méd. Belgique,' ix, 304; 'Jahrb. f. prakt. Pharm,' xxiv, 313; &c.]

This method, according to Stas, answers well for all the ALKALOIDS which are soluble in ether; including--ACONITIA, ANILINE, ATROPIA, BRUCIA, CODEIA, COLCHICINA, CONIA, DELPHIA, EMETINA, HYOSCYAMINE, MORPHIA (?), NICOTIA, PETININE, PICOLINE, SOLANINE, STRYCHNIA, VERATRIA, &c. By means of it Stas found nicotia in the heart-blood of a poisoned dog. With such alkaloids as are, however, only very sparingly soluble in ether (as morphia for instance), the result must, necessarily, be doubtful. To detect these, as well as all the alkaloids which are insoluble in ether, it is, therefore, necessary, as directed by Otto, to add to the alkaline fluid left by the decantation of the ether, sufficient solution of soda to dissolve the morphia, &c. (if any has separated), and after the expulsion of the last traces of the ether by a gentle heat, to add a concentrated solution of hydrochlorate of ammonia, and to allow the mixture to repose for some time in the open air. When MORPHIA is present, it separates under the form of small crystals.[22] Or the alkaline liquor may be diluted with distilled water, and treated with charcoal, and this with alcohol, in the manner noticed under method 4 (_below_).

[Footnote 22: Otto's 'How to Detect Poisons.']

4. (Graham and Hoffmann--slightly modified.) 2 or 3 oz. of purified animal charcoal are digested in about 1/2 gal. of the (neutral or only slightly acid) aqueous fluid under examination, with frequent agitation, for 10 to 12 hours, or longer. The liquid is then filtered, and the charcoal left on the filter is washed twice with cold distilled water. The charcoal is then boiled for 1/2 an hour with about 1/2 a pint of rectified spirit of 80 or 90%; the ebullition being conducted in a flask having a very long tube, open at both ends, fitted air-tight through the cork, to prevent loss of the alcohol by evaporation. The spirit, which now contains the alkaloid (if any was present in the original liquor), is next filtered whilst hot, and the filtrate is submitted to distillation until the whole of the alcohol is removed. A small quantity (commonly a few drops) of solutions of potassa is then added to the residual aqueous liquor, followed by 1 to 2 fl. oz. of pure ether, after which the whole is well agitated for several minutes, and allowed to repose for a short time. Lastly, the supernatant ether is decanted, and allowed to evaporate spontaneously, when the residuum (if any) left in the capsule may be tested by reagents, as before.

This method was devised for the detection of STRYCHNIA and NUX VOMICA in malt-liquors; but it is equally applicable to the detection of ANY ALKALOID which is soluble in ether. The CHARCOAL TEST may also be employed to detect alkaloids which are insoluble in ether; but then the base must be sought in the aqueous residuum obtained by the evaporation of the alcohol.[23]

[Footnote 23: 'Journ. of the Chem. Soc.,' v, 173.]

The presence of the alkaloids and their salts, in clear solutions, may be thus determined:--

I. (Fresenius).--1. The solution is rendered very slightly alkaline with dilute solution of potassa or soda, added drop by drop:--

a. No precipitate is formed; total absence of the alkaloids. (See 4, _below_.)

b. A precipitate is formed:--solution of potassa or soda is added, drop by drop, until the liquid exhibits a strong alkaline reaction:--

[Greek: a]. The precipitate redissolves; absence of Brucia, Cinchonia, Narcotina, Quina, Strychnia, and Veratria; probable presence of MORPHIA.

[Greek: b]. Precipitate does not redissolve, or not completely; probable presence of one or more of the first six of the above-named alkaloids:--the fluid is filtered from the precipitate, mixed with either bicarbonate of soda or of potassa, gently boiled nearly to dryness, and treated with water. If it dissolves completely; absence of morphia; an insoluble residue indicates MORPHIA.

2. The precipitate 1. _b._ [Greek: b]. is washed with cold distilled water, dissolved in a slight excess of dilute sulphuric acid, neutralised with a saturated solution of bicarbonate of soda, and allowed to repose a few hours:[24]--

[Footnote 24: Before setting the glass aside the liquor should be well mixed, and the glass stirrer vigorously rubbed against the sides of the vessel.]

_a_. No precipitate; absence of Cinchonia, Narcotina, and Quina:--the solution is gently evaporated nearly to dryness, and treated with cold water:--if it dissolves completely, pass on to 4; if there is an insoluble residue, it may contain Brucia, Strychnia, or Veratria. (See 3.)

_b._ A precipitate:--the filtered fluid is treated as directed at 2 _a_.; the precipitate is washed with cold distilled water, dissolved in a little hydrochloric acid, ammonia is added in excess, and subsequently a sufficient quantity of ether, agitation being had recourse to:--

[Greek: a]. The precipitate formed by the ammonia redissolves completely in the ether, and the clear fluid separates into two layers; absence of Cinchonia; probable presence of QUINA or NARCOTINA.

[Greek: b]. The precipitate produced by the ammonia does not redissolve in the ether, or not completely; probable presence of CINCHONIA, and perhaps also of Quina or Narcotina. The filtered liquid may be tested for these alkaloids as at _a_.

3. The insoluble residuum after the evaporation of the solution 2. _a._, or of the filtrate 2. _b._, is now dried in a water bath, and digested with absolute alcohol:--

_a._ It dissolves completely; absence of strychnia; probable presence of BRUCIA, QUINA (?), or VERATRIA:--the alcoholic solution is evaporated to dryness, and, if quina has been already detected, the residue is divided into two portions, one of which is tested for Brucia, the other for Veratria.

_b._ It does not dissolve, or not completely; probable presence of STRYCHNIA, and perhaps also of Brucia and Veratria:--the filtered fluid is divided into two portions, and tested separately as at _a_.

4. The original liquid 1. _a_. may contain Salicine, a proximate vegetable principle closely allied to the alkaloids:--a portion is boiled with hydrochloric acid for some time; the formation of a precipitate shows the presence of SALICIN. (See 2, _below_.)[25]

[Footnote 25: For further information on this subject, see the admirable 'System of Qual. Chem. Anal.,' by Dr C. R. Fresenius. Churchill.]

II. (Larocque and Thibierge.) Terchloride of gold is recommended, by these writers, as a more decisive test for the alkaloids than the 'double chloride of gold and sodium' commonly employed for this purpose. The following are the colours of the precipitates which it produces with the aqueous solution of their salts:--BRUCIA, milk-brown, passing into coffee-brown, and lastly chocolate-brown:--CINCHONIA, sulphur yellow:--MORPHIA, yellow, then bluish, and lastly violet; in this last state the gold is reduced, and the precipitate is insoluble in water, alcohol, the caustic alkalies, and sulphuric, nitric, and hydrochloric acid; it forms with aqua regia a solution which is precipitated by protosulphate of iron:--QUINA, buff-coloured:--STRYCHNIA, canary-yellow:--VERATRIA, pale greenish-yellow. All these precipitates, with the exception mentioned, are very soluble in alcohol, insoluble in ether, and only slightly soluble in water. Those with morphia and brucia are sufficiently marked to prevent these alkalies from being mistaken for each other; and those with brucia and strychnia are, in like manner, easily distinguishable.

III.--Mr Wanklyn discriminates the different alkaloids from the estimation of the ammonia they evolve. His process is as follows:--A small flask with a lateral tube, and connected with a Liebig's condenser, is charged with about 25 c. c. of an alkaline solution of permanganate potash made by dissolving 200 grammes of caustic potash and 8 grammes of crystallised permanganate of potash in 1 litre of water. A minute quantity of the alkaloid carefully and accurately weighed is now introduced, and the mixture slowly distilled. The most satisfactory results are obtained by treating from 1 to 5 milligrammes of the alkaloid in this way, but quantities so small as 1/10th of a milligram will in skilled hands give accurate results. The ammonia is formed in the distillate by Nesslerising it, as described under WATER ANALYSIS. For all practical purposes the poisonous alkaloids may be divided into four classes:

(a) Those which yield from 5 to 2 per cent. of ammonia.

(b) Those which yield from 2 to 3 per cent. of ammonia.

(c) Those which yield from 3 to 5 per cent. of ammonia.

(d) Those which yield a larger quantity than 5 per cent., _e.g._

I.

NH_{3} per cent.

SOLANINE yields half its nitrogen as Ammonia 0·98

II.

MORPHIA yields half its nitrogen as Ammonia 2·98

CODEINE, ditto, ditto 2·87

PAPAVERINE, ditto, ditto 2·50

VERATRIA, ditto, ditto 2·87

III.

ATROPIA yields all its nitrogen as Ammonia 5·73

NARCOTINE, ditto, ditto 4·11

STRYCHNIA yields half its nitrogen as Ammonia 5·09

BRUCINE, ditto, ditto 4·32

ACONITE, ditto, ditto 3·50

CONEINE, ditto, ditto 4·60

IV.

NICOTINE yields half its nitrogen as Ammonia 10·49

IV. Dr Guy, as well as others, have made researches, having for their object the determination of the exact temperature at which the poisonous alkaloids melt and sublime. A very minute speck of the substance is placed on a porcelain plate or copper disc, and a square or oval of microscope-covering glass is placed over it, supported by a thin ring of glass or any other convenient substance.

Heat is then applied to the plate or copper, and the temperature, as indicated by a thermometer at which the substance fuses or volatilises, is carefully noted.

CANTHARIDINE sublimes as a white Fahr. Cent. vapour without change of form or colour. 212° 100°

Sublime. Melt. /----------\ /----------\ Sublime, melt and Fahr. Cent. Fahr. Cent. MORPHINE } yield carbonaceous { 330° 165° 340° 171° STRYCHNINE} residue. { 345° 174° 430° 224°

Melt. Sublime. /----------\ /----------\ Fahr. Cent. Fahr. Cent. ACONITINE } { 140° 60° 400° 204° ATROPINE } Melt, change { 150° 66° 280° 138° VERATRINE } colour, sublime, { 200° 93° 360° 182° BRUCINE } and { 240° 116° 400° 204° DIGITALIN } deposit carbon. { 310° 154° 310° 154° PICROTOXIN} { 320° 160° 320° 160° SOLANINE } { 420° 215° 420° 216°

_Selmi's method of extracting poisonous alkaloids in forensic investigations._ The alcoholic extract of the viscera, acidified and filtered, is evaporated at 65° C., the residue taken up with water, filtered to separate fatty matters, and decoloured by means of basic acetate of lead, leaving the solution in contact with the air for 24 hours. It is then filtered, the lead precipitated by means of sulphuretted hydrogen, and the solution after concentration repeatedly extracted with ether. The ethereal solution is then saturated with dry carbonic anhydride, which generally causes a precipitate of minute drops adhering to the sides of the vessel, and containing some of the alkaloids. The ethereal solution is then poured into a clean vessel, mixed with about half its volume of water, and a current of carbonic anhydride passed for about twenty minutes, which may cause the precipitation of other alkaloids not precipitated by dry carbonic anhydride. Usually the whole of the alkaloids present in the ether are thrown down by these means, but if not, the solution is dehydrated by agitation with Barium oxide, and then a solution of tartaric acid in ether added to the clear liquid, taking great care not to employ excess of acid. This throws down any alkaloid that may remain. In order to extract any alkaloids that may still remain in the viscera, they are mixed with Barium hydrate and a little water, and then agitated with purified amylic alcohol; the alkaloids may subsequently be extracted from the alcohol by agitation with very dilute sulphuric acid.

A knowledge of the different solubilities of the alkaloids will be found an important auxiliary in their analysis. The following is a summary of the relative solubility of the most important of them. The figures denote the number of parts of the liquid required for their solution:--

_Absolute alcohol._--Strychnine insoluble; brucine soluble.

_Amylic alcohol._--Solanine (1061); digitalin sparingly soluble; morphine (133); strychnine (122); veratrine, brucine, atropine, aconitine, and picrotoxin, freely soluble.

_Benzol._--All the poisonous alkaloids, except solanine, are soluble in benzol.

_Chloroform._--Solanine (50,000); morphine (6550); strychnine (8); the rest freely soluble.

_Ether._--Solanine (9000); morphine (7725); strychnine (1400); aconitine (777); brucine (440); veratrine (108); atropine, picrotoxin,[26] and digitalin, very soluble.

[Footnote 26: Digitalin and picrotoxin, although not alkaloids, are inserted in the above list, because they have a general similarity in chemical properties to them; and for the convenience of the toxicologist.]

_Water_ (_cold_).--Strychnine (8333); veratrine (7860); morphine (4166); aconitine (1783); solanine (1750); brucine (900); atropine (414); picrotoxin (150); digitalin very soluble.

The principal Alkaloids and their Salts, in the state of powder, or with 'conia' and 'nicotia,' in the state of an oily looking liquid, may be thus distinguished:--

1. _a._ The powder is treated with nitric acid:--It is coloured red; probable presence of Brucia, Delphia, Morphia, or commercial Strychnia. If the reddened acid becomes violet on the addition of 'protochloride of tin,' it is BRUCIA; if it becomes black and carbonaceous, it is DELPHIA. If the powder is fusible without decomposition, and strongly decomposes iodic acid, it is MORPHIA; if it is not fusible without decomposition, and does not decompose iodic acid, it is STRYCHNIA.

_b._ If instead of a red, the powder strikes a green colour with nitric acid, it is SOLANIA; if it is insoluble in 'ether,' and not reddened by 'nitric acid,' it is EMETIA; if soluble in ether, not reddened by 'nitric acid,' but melts and volatilises when heated, it is ATROPIA; if it is thus affected by ether or nitric acid, but does not volatilise, it is VERATRIA. (See 2, _below_.)