On Anhalonium Lewinii

On Anhalonium Lewinii

By Dr. L. Lewin, Docent at the University of Berlin.

I have already pointed out on several occasions that most of the plants which the uncivilized peoples of the earth have discovered over the millennia as remedies, stimulants and poisons, without any experimental basis and guided only by a kind of instinct, and which they used and still use, offer through this empirical foundation a certain guarantee of their efficacy; for whenever such substances have been re-examined with our modern means of investigation, what was expected has usually been confirmed. We have no idea how these peoples acquired such knowledge. Livingstone already remarked, when speaking of the Kombi poison: "It is difficult to conceive by what sort of experiments the properties of these poisons, known for generations, were proved. Probably the animal instincts, which have become so obtuse by civilization, that children in England eat the berries of the deadly nightshade (Atropa Belladonna) without suspicion, were in the early uncivilized state much more keen ....... In like manner, the earlier portions of the human family may have had their instincts as to plants, more highly developed than any of their descendants — if indeed much more knowledge than we usually suppose be not the effect of direct revelation from above."

However that may be, the search for such substances usually promises success, and so I gladly undertook to examine a drug which the firm of Parke, Davis & Co. had received from Mexico and was kind enough to hand over to me during my stay in America. The drug, whose place of origin is kept secret, is said to be called "Muscale Buttons" in its homeland and to be sold and used as a narcotic stimulant. The botanical examination made in America established only that it belonged to the cacti; a closer assignment to a genus was not possible there. After my return I turned to Herr Hennings of the botanical museum here, and he succeeded, as I later did myself, in finding flowers in the drug that now allowed a precise determination. It turned out to be an Anhalonium, and indeed a new species close to Anhalonium Williamsii. In the meantime I had recognized quite peculiar effects in this plant, and for this reason Herr Hennings did me the honour, for which I thank him here, of giving this species my name.

This new species joins the six Anhalonia already known as the seventh. That it remained unknown for so long is no surprise in the case of Anhalonium in particular, for these plants inhabit the highest rocky mountains and sit on hard-to-reach limestone ledges, into which they penetrate deeply with their long, turnip-shaped roots. As Lemaire already noted, this genus of melocacti differs from all other cacti in its natural habitat; for the others thrive fairly well in our cultivation, even in the north, while the Anhalonia alone do poorly.

[Omitted here: the section "Historical and general remarks on cacti" (pp. 402–405), a survey of cacti in classical sources (Pliny, Hermolaus Barbarus on Dioscorides), of earlier chemical work by Buchner and Descourtilz, and of cacti used as food, drink and medicine, chiefly in the Antilles and the American Southwest.]

This exhausts what was previously known about the pharmacological or toxic action of cacti, so far as I have searched the literature on the point. The following findings, which I regard and publish as preliminary, depart substantially from it. The investigation can be fully completed only after some time, and until then I expressly reserve further work on this subject for myself.

Preliminary remarks on the chemical behaviour of Anhalonium Lewinii

To obtain a pure substance I applied a whole series of methods (precipitation of the aqueous extract with lead, also with tannic acid, phosphotungstic acid, etc.) without obtaining sufficient usable quantities of pure material. The aqueous extract is yellowish brown, strongly mucilaginous, has little odour, and tastes intensely and lingeringly bitter. It contains no tannic acid and gives precipitates with the usual alkaloid reagents.

[Omitted here: Lewin's three extraction procedures and his description of the resulting alkaline syrup (p. 406).]

I shall provisionally call this basic syrupy substance anhalonine. I will give a fuller characterization of it and of its salts as soon as I have prepared more of it.

[Omitted here: the properties of a crystalline salt of the base and a table of its reactions with alkaloid reagents (pp. 407–408).]

Action of Anhalonium Lewinii and of anhalonine

The very first experiments, which I made with concentrated decoctions on cold- and warm-blooded animals, revealed the unexpected and surprising fact that this is an extraordinarily poisonous substance.

If even a few drops of such an aqueous extract are injected under the skin of frogs, the animal's appearance changes almost as soon as the needle is withdrawn. Its flanks fall in or are drawn in. Where a moment before the belly skin bulged out on both sides in its familiar curve, there are now deep hollows. The backbone stands out strangely as a sharply defined ridge. This gives the animal a mummified look. At the same time as this change, or immediately after it, the frog raises itself on its four limbs, which likewise suddenly look peculiarly thin and wasted, stands motionless for a while like a quadruped, and then crawls about in the same posture. After 5–10 minutes, sometimes sooner, this state passes; the animal squats again in its normal position, though still looking collapsed, and after a further interval its appearance and posture are normal again. These changes occurred almost every time in the many experiments I made. They appear to be an acute muscular spasm (of the diaphragm, abdominal muscles, etc.). Once this spasm has passed, a varying length of time elapses, depending on the potency of the preparation used, before heightened reflex excitability appears. Exactly as after strychnine poisoning, the frog then starts at the lightest touch, spreads its toes and stretches its webs as far as they will go. This stage lasts for varying periods. If the doses were small, it can be observed for 5–8 days. Usually, however, the condition rises to such a pitch that any external stimulus, however slight, produces a typical reflex tetanus in which the head is drawn back, so that the body is bent into a concave arch and appears board-hard. Only after mild poisoning did I see the animals resume their normal posture after such a tetanus; mostly they remained in the position they had taken during it.

I was sometimes struck by the animals' remarkable resistance to the fairly frequent convulsive attacks. In some experiments, however, death came quickly after reflex excitability had steadily declined.

Tetanus can still be produced in the body even after the animal has been decapitated. In a large series of experiments this ceased to be possible when I cut the spinal cord below the fifth vertebra; in others this was not the case. Prior section of the iliac plexus on one side meant that the corresponding leg took no part in the convulsion. I did not see the poison affect the heart rate.

I observed entirely identical effects on injecting the alcoholic extract dissolved in water, and other preparations, some of which have been described above.

By subcutaneous administration of anhalonine in a clear, colourless or yellowish, acid aqueous solution I likewise produced in frogs the primary sunken state and the stage of heightened reflex excitability and tetanic convulsions.

Pigeons given 1–2 Pravaz syringes subcutaneously of the concentrated aqueous acid extract of the plant, warmed and shaken with charcoal, begin to vomit a few minutes later. I have seldom seen more convulsive and persistent vomiting in pigeons. In the intervals between bouts of vomiting the wings are spread from time to time with a short jerk. The bird squats with its wings either folded or spread. It starts when the cage is jarred. After 12 minutes it beats its wings convulsively, falls over, stretches out its legs and opens its beak wide while the head is drawn back. This first attack passes, but the pigeon cannot right itself again, and after the attacks have recurred several times it dies, either during one or in an interval free of convulsions.

At dissection the heart was found arrested in diastole, with only slight fibrillation of the atria, which soon ceased.

If the dose of poison was not large enough, no symptom of poisoning appears other than vomiting. I poisoned some pigeons 6–10 times on different days without observing any effect but vomiting.

With anhalonine sulphate, too, I was able to produce vomiting after subcutaneous administration. I have not so far had larger amounts at my disposal, so I cannot say whether these would also produce tetanic convulsions. I saw one young pigeon die about 6 hours after poisoning with this substance, with narcotic symptoms accompanied by slight convulsive movements of the head recurring from time to time.

In rabbits, purely aqueous extracts given by stomach in amounts of 12 g, aqueous solutions of alcoholic extracts given subcutaneously in doses of 2–3 Pravaz syringes, and other preparations produced pictures of poisoning in no way different from those produced by administering strychnine or brucine. The effect is much slower from the stomach than after injection into the subcutaneous tissue. In one rabbit it appeared only after 4 hours. The animal trembled all over, as far as the body could be seen. But the moment I tried to take it out of the cage, it went into a typical reflex tetanus. The limbs are stretched and the head drawn back onto the neck. The attack passes. The animal resumes its crouching position. Breathing is very rapid. The forepaws slip, the head falls to the floor. A second attack soon follows, to which the animal succumbs. The heart still beats fairly vigorously after breathing has stopped.

I shook the alkalinized, concentrated ether extract of the alcoholic extract of the plant with petroleum ether, drove this off, dissolved the faintly yellow residue in acidified water, and injected it into a rabbit. Here tetanus set in after only 12 minutes. The trembling animal rose stiffly on its paws, went into tetanus, and died after the third attack.

This demonstrates for the first time that a cactus possesses extraordinarily violent general toxic effects. The next task will be to clarify the chemistry of this Anhalonium further and then to proceed to the examination of other Anhalonia. It also remains to be investigated in what way, for what purposes and to what extent these "Muscale Buttons" are used as a stimulant. I hope to be able to give information on this before too long.