Besides acid and basic substances, plants furnish a large number of proximate principles which are chemically neutral. Their names end in in (Latin, inum), in accordance with the pharmacopaeial rule to distinguish them from alkaloids, as stated above. The most important are the glucosides (glycosides).

The glucosides are a class of bodies which, under the influence of certain agents, decompose and yield some form of sugar, together with one or more other bodies. These decomposing agents may be heat, dilute acids, strong alkalies, enzymes, bacteria, or fungi. Most of the glucosides yield glucose, whence the name; a few of them yield other sugars. Chemically, they are a loose group, and beyond their readiness of decomposition and their power to yield sugar, have no essential characters in common. They follow no rules as to solubility, or taste, or importance, some of them being bitter, some not; some soluble in water or alcohol, some not; some inert pharmacologically, and others, such as the active principles of digitalis, strophanthus, and cascara, being among our most valued remedies. The only glucosides official in the United States Pharmacopoeia are salicin, the active principle of willow and poplar barks, and strophanthine the active principle of strophanthus. The gluco-sidal nature of these bodies may be readily shown, for if they are warmed with dilute hydrochloric acid, the mixture will give the glucose test with Fehling's solution. The products of the decomposition of salicin are glucose and saligenin (salicyl alcohol).

C6H11O5.O.C6H4Ch2oh +

H2O

=

C6H12O6 +

C6H4.OH.Ch2oh

Salicin

Glucose

Salicyl alcohol

The ready decomposition of these bodies indicates that preparations of drugs such as digitalis, which depend upon glucosides for their activity, must neither be mixed with strong alkalies or acids nor subjected to continued heat.

There are two glucosides, amygdalin and sinigrin, which are practically inert pharmacologically, but are of great importance because of the products of their decomposition by certain enzymes.

Amygdalin, with its particular enzyme, emulsin, occurs in bitter almonds, peach-pits, wild-cherry bark, and cherry-laurel leaves. In the presence of water the enzyme emulsin acts upon the amygdalin, causing it to split up into glucose, hydrocyanic acid (prussic acid), and benzaldehyde. The mixture of the two latter constitutes the highly poisonous volatile "oil of bitter almond," which is required by the Pharmacopoeia to contain not less than 85 per cent, of benzaldehyde and not less than 2 per cent, nor more than 4 per cent, of hydrocyanic acid.

Amygdalin

Water

Glucose

Prussic acid

Benzaldehyde

C20H27No11.3H2O +

2H2O

=

2C6H12O6 +

Hcn +

C6H5Coh +

3H2O

The amygdalin occurs in bitter almond to the extent of 1.75 to 3 per cent., so that one ounce of bitter almonds would be a poisonous dose. As enzymes are destroyed by heat and rendered inert by alcohol, no preparation of bitter almond, wild-cherry bark, or cherry-laurel leaves should be made until the drug has first been steeped in lukewarm or cold water to permit this enzyme action and the development of these products. If the crude drug should be extracted in the usual way by alcohol or very hot water, without preliminary steeping, the preparation would be inert. Sweet almonds also contain emulsin, but no amygdalin, hence are inert pharmacologically and may be swallowed ad libitum.

Sinigrin, with its peculiar enzyme, myrosin, occurs in black mustard seed, and to some extent in horseradish root. Mustard flour, as purchased, contains nothing irritating, and has the odor of ordinary flour; but as soon as it is mixed with water, it develops the odor and irritant properties characteristic of mustard. This is because, in the presence of water, the myrosin acts upon the sinigrin and splits it up to yield glucose, potassium bisulphate, and allyl isothiocyanate, the last-named substance being the highly irritating "volatile oil of mustard."

Sinigrin

Glucose

Potassium bisulphate

Allyl isothiocyanate

C10H18Ns2o10k

=

C6H12O6 +

Khso4 +

C3H5Cns

As this enzyme is rendered inert by a temperature above 60° C. (140o F.), very hot water should not be used in preparing a mustard poultice or a mustard foot-bath. It is of interest that this volatile oil of mustard, when shaken with alcohol and ammonia water, deposits more than its own weight of crystals of thiosinamine, a drug which has been used by injection for the removal of excessive scar tissue. (See Part II.)

C3H5Cns + Nh3 = C3H5Csn2h3.

White mustard seed also contains myrosin, but instead of sinigrin, it contains another glucoside, sinalbin. Under the influence of myrosin in the presence of water sinalbin splits up into entirely different products, viz., glucose, sinapine sulphate (an alkaloidal salt), and acrinyl isothiocyanate (an irritant but non-volatile oil).

Phlorhizin (phloridzin or phlorizin) is a glucoside obtained from the bark of apple, pear, cherry, and plum trees, especially the bark of the root. It is nearly insoluble in cold water, but readily soluble in alcohol and alkaline liquids. Its administration is followed by glycosuria without hyperglycemia, the glycosuria resulting from changes in the kidneys by which they are made unable to keep back the normal sugar in the blood; in fact, there is a hypoglycemia. In other words, the "secretion threshold" of the kidneys for sugar (Magnus) is lowered. Phlorhizin is diuretic, this action, according to Loewi (1903), being due to the prevention of kidney reabsorption by the sugar of the urine. It has been used as a test of the functional power of the kidneys.

Besides the glucosides, there are other neutral principles of importance in medicine, such as santonin, aloin, elaterin, chrysarobin, etc. Some of those whose chief characteristic is bitterness, as quassin of quassia, and chamomillin of chamomile, are often spoken of as bitter principles or amaroids.