This group of purgatives, as far as its general properties are concerned, is so well described in many text-books that it is unnecessary here to go into the details of their preparation and the commoner characteristics of each. Certain points which have come up in connection with my own experiments, however, may be briefly described here.

Cascara Sagrada is prepared in many ways, but the most favorable preparation for experiment is the dried extract. This is the dark yellow powder familiar in commerce. It is found that in shaking this powder in distilled water it is almost entirely insoluble. The result is a dirty yellow mixture, the filtrate from which gives an acid reaction. This suggested neutralizing the mixture or making it alkaline. A small amount of sodium bicarbonate was added, and the powder immediately went into solution, producing a clear dark brown fluid.[92] A similar result was obtained by adding sodium hydrate. It was found that ¹⁄₂ g. of the dried extract could be dissolved in 25 c.c. m/24 NaHCO₃. This solution in NaHCO₃, is practically neutral. If a few drops of dilute H₂SO₄ be added a yellow precipitate at once appears giving a mixture or suspension similar to that originally obtained by adding the powder to distilled water. The addition of NaHCO₃ will again produce the characteristic dark brown solution. The extract is much more readily soluble in a stronger solution of NaHCO₃.

The dried extract is thus soluble only in a neutral or alkaline fluid. It is insoluble in distilled water on account of the free acid which is present in the powder.

Cascara extract is readily soluble in the intestinal juice of a rabbit, a characteristic dark brown clear solution being obtained. On the other hand, it is insoluble in the gastric juice, and an alkaline solution added to the gastric juice is at once precipitated.

It was found that the intravenous injection of 1 c.c. of a 2% solution of cascara extract in m/25 NaHCO₃ produces within a minute very strong peristaltic movements in the intestine. A similar injection of the same amount of m/25 NaHCO₃ alone produces no such result, though stronger solutions of NaHCO₃ cause a slight increase in intestinal movements. It is therefore the cascara in solution which produces these strong contractions.

A somewhat larger quantity of the cascara solution injected subcutaneously produces increased peristaltic activity after an interval of several minutes.

If the cascara solution be applied directly to the serous surfaces of the intestine, very strong contractions and peristaltic movements result in 2 or 3 minutes. A solution of m/25 NaHCO₃ alone produces very slight movements when applied in this way. These can, however, be readily distinguished from those produced by cascara. The latter are much more powerful, are slower in developing, and can be only partially inhibited by m/6 CaCl₂. The movements following the application of pure NaHCO₃ solution, however, are weak, they appear almost immediately, and can be entirely suppressed by the application of m/6 CaCl₂ solution.

When the cascara solution is placed in the stomach no movements appear in the intestine even after 15-30 minutes. The acid of the gastric juice has evidently precipitated the cascara, which cannot act until it is passed on into the intestine where it may be dissolved in the alkaline juice of the intestine. If instead of placing the solution in the stomach it is injected directly into the small intestine, increased peristaltic movements begin within 5 minutes. Here it evidently remains in solution and is absorbed. It is for this reason that in human beings cascara taken by mouth acts only after several hours. It is precipitated in the stomach and must reach the intestine before it is dissolved and absorbed.

In addition to the increased peristaltic activity caused by the cascara, there seems to be also an increase in the secretion of fluid into the lumen. One or two hours after the injection 20-30 c.c. fluid could be collected from the small intestine. Without the purgative it is rarely possible to obtain more than 5 to 10 c.c.

It was found that calcium chloride has only a very transient effect in inhibiting the increased movements produced by cascara. For 2 or 3 minutes following the injection of CaCl₂ the movements were usually quieted, but they rapidly began again and continued as vigorously as before.

The behavior of rhubarb is in every way similar to that of cascara. It is less readily soluble, but the solution acts in a way quite like that described for cascara.

It is further well known that aloin injected subcutaneously causes increased peristalsis. A study has recently been made of certain constituents of the derivatives of the aloes group of purgatives. Esselmont,[93] following the work of Tschirch,[94] experimented with a number of substances obtained from these purgatives. Aloëemodin is present not only in aloes, but also in Cascara sagrada and senna leaves. A small amount of this substance acts as a purgative. Alochrysin, aloingrin, barbaloin, all act as purgatives. Chrysophanic acid, which is found in aloes, rhubarb, and senna is a mild purgative. It is of interest to note that each of these substances is either a di-or tri-oxymethylanthrachinon. They owe their purgative action, according to Tschirch, to their containing the oxymethylanthrachinon group.

Some experiments[95] which I recently made on a jellyfish (Polyorchis) with some of the vegetable purgatives are of interest. They were suggested by the experiments of Loeb[96] on the effect of various salts on the isolated center of the animal and of a related form (Gonionemus). When separated from the margins the bell-like centers of these jellyfish do not beat in pure sea-water. In case of Gonionemus it was found that the addition of one of a number of salts (calcium precipitants) caused the center to beat. This group of salts includes the so-called saline purgatives.

The methods used in the experiments with vegetable purgatives were practically the same as those used by Loeb. The animal was bisected just above the ring of sense organs in order to entirely remove the margin containing the main nervous system. The center was then placed in mixtures of sea-water and solutions of the purgatives. The center never beats in pure sea-water, but was found to beat vigorously in sea-water to which a small quantity of a solution of cascara, rhubarb, aloin, podophyllin, or colocynth had been added. It was necessary to dissolve the cascara and rhubarb extracts in m/24 NaHCO₃, since they are not soluble in pure water. The centers do not beat in sea-water to which pure m/24 NaHCO₃ has been added in quantities equivalent to those added with the purgative solution.

A solution of ¹⁄₄ g. cascara extract was made in 50 c.c. m/24 NaHCO₃. It was found that a mixture of 25 c.c. sea-water + 2 c.c. of this cascara solution was the most favorable for producing rhythmical contractions in the isolated center of Polyorchis. Contractions lasted 10-15 minutes.

A solution of rhubarb extract of the same strength was made. The optimal mixture in this case is 25 c.c. sea-water + 0.5 c.c. or 1 c.c. rhubarb solution. In this mixture the contractions develop quickly and last 15 minutes or more.

With aloin the concentration of the purgative needed to produce optimal results was somewhat greater than in cascara or rhubarb. Colocynth and podophyllin act similarly, but the contractions soon cease.

These vegetable purgatives thus act on the jellyfish, Polyorchis, in a way quite similar to that described by Loeb for saline purgatives.

Pilocarpine, though not used as a purgative on account of its special action on other organs of the body, has a powerful action also on the intestine. Its influence on the intestine is much like that of barium chloride. It causes violent contractions of the musculature of the gut and very active peristaltic movements. This is the case in whatever way the substance is administered. A few drops of a ¹⁄₁₀% solution of pilocarpine hydrochlorate in distilled water poured on the serous surfaces of the rabbit’s intestine brings about almost immediately violent peristaltic movements. In addition to this there is an increase in the amount of fluid secreted into the intestine, 20-30 c.c. gathering in the small intestine in an hour. The evacuation of faeces takes place in about three-quarters of an hour. These may be of a semifluid character, and with larger doses resemble the faeces produced by BaCl₂. The antagonism between pilocarpine and CaCl₂ is incomplete. CaCl₂ is capable of inhibiting only temporarily the movements caused by pilocarpine.

It is interesting to note the marked purgative effect of pilocarpine in a small fresh-water crustacean (Sida crystallina). This animal, which has been spoken of in previous chapters belongs to the Cladocera. The intestine extends in a fairly straight line throughout the body, bending downward at the post abdomen to open to the outside. At the anterior end is a slight dilatation which may represent the stomach. From this there open two diverticula or coeca which seem to be of a glandular nature, and are sometimes spoken of as digestive glands. They are usually filled with a greenish fluid. The intestine is always filled with brown faeces which are normally expelled in small quantities, only at considerable intervals. Slight peristaltic waves are commonly seen in the lower part of the intestine.

These animals were placed in various solutions, and it was found[97] that pilocarpine hydrochlorate, aloin, cascara, as well as barium chloride, sodium citrate, sulphate, and fluoride, caused an increased peristaltic activity of the intestine, and a rapid expulsion of faeces, so that in a very short time the entire intestine was empty. At the same time the intestine becomes filled with a greenish fluid similar to that seen in the diverticula. This fluid may be also expelled and replaced again. It is evidently secreted by the intestine or by the diverticula as a result of the purgative action. Very dilute solutions of pilocarpine are sufficient to bring about this effect. In a 1% solution the action is very rapid, and evacuation of faeces may be brought about by a mixture of 1 c.c. 0.1% pilocarpine in 10 c.c. water. This takes place within 20 minutes.

An attempt was made to determine whether or not CaCl₂ is capable of inhibiting the action of pilocarpine. The experiments on rabbits in this respect were unsatisfactory. It was found that the greatest dilution at which expulsion of faeces in Sida could be caused in a short period of time was 1 c.c. 0.1% pilocarpine + 10 c.c. water. Animals were placed in a mixture of 1 c.c. 0.1% pilocarpine + 10 c.c. m/6 CaCl₂. These behaved exactly as though the water had not been replaced by CaCl₂. In other words, the presence of the CaCl₂ did not delay at all the action of the pilocarpine. This was repeated many times, and it seems that in Sida at least the action of pilocarpine is not at all antagonized by calcium chloride. In a mixture, however, of 10 c.c. 1% atropin sulphate + 1 c.c. 0.1% pilocarpine no evacuation of faeces took place and there was no increase in peristalsis.