The Action of Purgatives of Vegetable Origin.
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 NaHCO_{3}. This solution in NaHCO_{3}, is practically
neutral. If a few drops of dilute H_{2}SO_{4} 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 NaHCO_{3} will again produce the characteristic dark
brown solution. The extract is much more readily soluble in a stronger
solution of NaHCO_{3}.
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 NaHCO_{3} produces within a minute very
strong peristaltic movements in the intestine. A similar injection of
the same amount of m/25 NaHCO_{3} alone produces no such result, though
stronger solutions of NaHCO_{3} 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 NaHCO_{3} 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 CaCl_{2}. The movements following the application
of pure NaHCO_{3} solution, however, are weak, they appear almost
immediately, and can be entirely suppressed by the application of m/6
CaCl_{2} 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 CaCl_{2} 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 NaHCO_{3}, since they
are not soluble in pure water. The centers do not beat in sea-water to
which pure m/24 NaHCO_{3} 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
NaHCO_{3}. 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 BaCl_{2}. The antagonism between pilocarpine and CaCl_{2}
is incomplete. CaCl_{2} 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 CaCl_{2} 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 CaCl_{2}. These behaved exactly as though the water had not been
replaced by CaCl_{2}. In other words, the presence of the CaCl_{2} 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.
FOOTNOTES:
[92] MACCALLUM, J. B.: University of California Publications,
Physiology, Vol. I, p. 163.
[93] Archiv f. exp. Path. u. Pharm., Bd. 43, 1900, S. 274.
[94] Schweiz. Wochenschrift für Chemie and Pharmacie, 1898, No. 23.
[95] To appear shortly in Journal of Biological Chemistry.
[96] _Loc. cit._
[97] MACCALLUM, J. B.: University of California Publications, Vol. II,
1905, p. 65.
Transcriber’s Notes
Punctuation and spacing errors have been corrected.
Page 33: In the footnote, “no interval beteen” changed to “no interval
between”