These are a class of organic bodies of alkaline reaction, composed of carbon, hydrogen, and nitrogen, and sometimes other elements. The class includes a great many of our most powerful drugs. Their basic or alkaline nature gives the name alkaloid {alkali and eidos, resembling). They possess the power of neutralizing acids with the formation of salts, and in doing so take up the acid without the liberation of hydrogen. In this respect they resemble ammonia, and differ from the alkali metals.

Na + Hc1 = NaCl + H. Nh3 + Hc1 = Nh3.Hci C21h22n2o2 (strychnine) + Hc1 = C21H22N2O2.HCl

Some of the alkaloids are strongly basic, while others, such as caffeine, are so feebly basic that they are with difficulty made to form salts at all. Most are monacid, uniting one molecule of the alkaloid for each basic hydrogen in the acid. A few are diacid. Quinine forms two different salts with acid, those with sulphuric acid, for example, being quinine sulphate, the neutral sulphate, in which two molecules of quinine unite with one molecule of the dibasic sulphuric acid, (C20H24N2O2)2.H2So4+7H2O, and quinine bisulphate, the acid sulphate, in which only one molecule of quinine unites with each molecule of sulphuric acid, C20H24N2O2.H2So4+7H2O. The uncombined alkaloids, to distinguish them from the "alkaloidal salts," are known as "pure alkaloids," and are not much employed.

Nomenclature

To distinguish these basic substances from the neutral principles, the United States Pharmacopoeia makes all the names of alkaloids end in ine (Latin, ina), as quinine (quinina), cocaine (cocaina); and the names of the neutral principles end in in (Latin, inum), as digitalin (digitalinum), salicin (salicinum). This is a simple device for distinction, and it serves a good purpose. It is to be regretted that this distinctive spelling is not followed in all the text-books. The old form, ending in ia, as quinia, morphia, strychnia, is now obsolete.

Solubility

The pure alkaloids are, as a rule, not readily soluble in water, but they dissolve more or less readily in alcohol, ether, chloroform, and the fixed and volatile oils. The alkaloidal salts, on the contrary, are mostly quite soluble in water, and fairly so in alcohol, but dissolve with difficulty in ether, chloroform, and the oils. For example, atropine, the pure alkaloid, is soluble in 455 parts of water, in 1.5 parts of alcohol or chloroform, and in 25 parts of ether; while atropine sulphate, the salt in common use, is soluble in 0.38 part of water (less than its own weight); in 5 parts of alcohol, in 420 parts of chloroform, and in 3000 parts of ether. Commonly in practice we employ the salts only, but when a solution is to be made in oil, or chloroform, or ether, we must use the pure alkaloid.

Incompatibles

Alkaloids have extensive chemic affinities, and there are many reagents which are used in the laboratory as tests or precipitants for them. As physicians, however, we need know only their common prescription incompatibles, i. e., those substances which form precipitates with alkaloidal salts, and which we would be likely thoughtlessly to include in a prescription containing an alkaloidal salt. Such common prescription incompatibles are:

1. Alkalies, which combine with the acid radicle and throw the less soluble pure alkaloid out of solution (some of the alkaloids are destroyed by strong alkalies).

2. Tannic acid, which forms the comparatively insoluble tannate.

3. Iodine, iodides, and bromides, which form the comparatively insoluble iodides and bromides, or double salts.

4. Mercuric chloride, which forms insoluble double salts. In these cases it must be borne in mind that the alkaloid is merely rendered less soluble in water, so if a large volume of water or a fair percentage of alcohol is present, the precipitation may not occur.

Physical Character

Most of the alkaloids are solids, as morphine, quinine, and strychnine. A few of them are volatile liquids, as nicotine, pilocarpine, coniine, and lobeline, but these latter mostly form non-volatile solid salts, which can be readily handled. Some are crystalline, some amorphous. Some are deliquescent and liquefy in moist air, as pilocarpine hydrochloride; others are efflorescent and lose weight in dry air, as the sulphate of strychnine and the sulphate of quinine. Some are decomposed by the heat of boiling water; others can stand much higher temperatures. Cocaine is decomposed at about 980 C. (just below the boiling-point of water), and its solutions cannot, therefore, be sterilized safely by boiling. Some which will stand a higher temperature for a short time are: aconitine, atropine, brucine, cevadine, codeine, morphine, narcotine, and strychnine; so that aqueous or alcoholic liquids containing these alkaloids may be brought to the boiling-point without fear of harm.

Taste

The taste of alkaloids is bitter - that of strychnine and quinine intensely so; that of morphine, codeine, and caffeine mildly so.

Occurrence

Alkaloids occur almost wholly in the higher plants - the dicotyledons. A few are found in the lower plants, and one of these, muscarine, is the poisonous principle in a few of the poisonous mushrooms. Some plants furnish many alkaloids, opium, for example, yielding about nineteen, and cinchona about thirty-two. In some cases one alkaloid is found in one part of the plant and another in a wholly different part of the same plant; often several are found together. Where a number of alkaloids occur in one plant they are usually closely related, both chemically and pharmacologically, as in the case of the alkaloids of belladonna; but in some instances they are quite different and may even be pharmacologically antagonistic, as physostig-mine and calabarine in the Calabar bean.

It is of interest that some alkaloids are confined entirely to one botanical family, as atropine, which is not found outside of the potato family (Solanaceae); or to one plant genus, as pilocarpine; or to a particular species, as morphine in the oriental Poppy and even then, perhaps, only when it is grown in a particular region. Others, however, are of wider distribution, as caffeine, which is found in various parts of the world in wholly unrelated plants, and berberine, found in the northeastern region of the United States in the barberry, hydrastis, and moonseed.

The amount of alkaloid present in different specimens of a drug may vary within wide limits, as might be expected in plants growing under such different conditions of soil, climate, and weather, and subjected to different methods of collecting, drying, preserving, etc. Yet the best quality of most drugs is notably uniform in its alkaloidal content.

Alkaloids produced by animals are more commonly known as leukomains and ptomains - leukomains, when they are formed by the body-cells, that is, are products of metabolism, for example, epinephrine; and ptomains, when they result from micro-bic decomposition of dead material, especially the amino-acids. Ptomain-poisoning from decomposing foods may closely resemble poisoning by plant alkaloids; in fact, one ptomain is called ptomatropine, because it gives the symptoms of atropine poisoning. Certain of the alkaloids, as choline, neurine, xanthine, and some of the ptomains are produced by both plants and animals, so that the dividing-line is artificial and not based on chemic nature.

Artificial Alkaloids

A number of alkaloids can be prepared artificially, and theophylline, which occurs naturally in minute quantity in tea-leaves, was the first to be produced synthetically on a commercial scale. Suprarenine, a synthetic with the actions of epinephrine, is also marketed. In addition, the Pharmacopoeia recognizes four bodies which are manufactured from plant alkaloids, viz., apomorphine, prepared from morphine by dehydration; cotarnine, prepared by hydrolizing narcotine; homatropine, which results from the action of mandelic acid upon tropine, the mother-substance of atropine; and hydrastinine, obtained by the oxidation of hydrastine. Two other artificial substances of the Pharmacopoeia, hexamethylenamine, or urotropine, and antipyrine, have close chemic affiliations with the alkaloid group.

That there may be differences in the physiologic actions of the different salts of an alkaloid is suggested by the experiments of O. H. Brown, 1907, on paramcecium. For example, in n/200 solutions of quinine salts the paramoecia lived in the sulphate thirty seconds, in the chloride, thirty seconds, in the hypo-phosphite, fifteen seconds, in the bisulphate, three hundred and thirty seconds. In n/500 solution of strychnine salts they lived in the acetate five seconds, in the nitrate, forty-five seconds, in the sulphate, seventy seconds, in the hypophosphite, seven hundred and twenty seconds. They were less readily poisoned by n/100 solutions of morphine salts, so the percentage of paramcecia dead at the end of a given time was taken. At the end of two hours, of those in the acetate none were dead, while of those in the valerianate 5 per cent., of those in the sulphate 60 per cent., and of those in the meconate 90 per cent., were dead.