ALKALOIDS OF THE POISONOUS MUSHROOMS.
Schrader, after some experiments made in 1811, stated that the poisonous principle of the "Fly mushroom," Amanita muscaria, seemed to be combined with its red coloring matter and might be extracted by water or aqueous alcohol, but that it was not soluble in ether.
Vaquelin, as the result of more extended investigations made in 1813, expressed the opinion that this poison was not confined to the coloring matter of the mushroom, but that it was an integral part of the fatty constituents not only of muscaria but of several species of mushrooms. In 1826 and 1830, and again in 1867, important investigations were made and published by Letellier relating to the medical and poisonous properties of mushrooms growing around Paris. Letellier's early investigations led him to the conclusion that there were two poisons contained in certain fungi—(1) an acrid principle easily destroyed by drying or boiling or by maceration in alcohol or in alkaline solution, and (2) a peculiar poisonous alkaloid found only in certain of the Amanita group. Letellier in 1866 named this latter alkaloid amanitin. He then considered it to be the active poison of Amanita muscaria, Amanita phalloides, and Amanita verna, but a subsequent analysis by the German chemists Schmiedeberg and Koppe showed the amanitin of Letellier to be identical with cholin, a substance found in bile. Kobert says that amanitin is non-poisonous in itself, but states that it may be changed on decay of the mushroom to the muscarin-like acting neurin, which is highly poisonous. He thinks it highly probable that nearly all of the edible and non-edible mushrooms contain pure amanitin (cholin) partly in primitive condition and partly in a more intricate organic connection, as lecithin. It has been demonstrated that amanitin separates very readily from lecithin during the decay or careless drying of mushrooms and changes into the poisonous neurin; hence the necessity of using mushrooms only when perfectly fresh or when quickly dried.
Muscarin.[A]
[A] The earliest account of the separation of the poisonous principles of the mushrooms of the genus Amanita dates back to the experiments of Apoiger in 1851. Harnack's researches were published in 1876 and those of Huseman in 1882.
To the eminent German chemists Schmiedeberg and Koppe is due the credit of isolating the active poisonous principle of the Fly mushroom (muscarin). These authors published in 1869 a series of interesting experiments made with muscarin, having relation to its effect upon the heart, respiration, secretions and digestive organs, etc., and this was supplemented by other experiments made by their pupils, Prof. R. Boehm and E. Harnack. Schmiedeberg and Koppe's work relates to the effect of this poison on man as well as upon the lower animals. Dr. J. L. Prevost in 1874 reviewed the investigations made by Schmiedeberg and Koppe in a paper read before the Biological Society of Geneva, adding some confirmatory observations of his own relative to experiments made with muscarin upon the lower animals. The experiments made by these authors demonstrated "that muscarin arrests the action of a frog's heart, that a muscarined frog's heart began to beat immediately under the influence of atropin, and further that it was impossible to muscarine a frog's heart while under the influence of atropin."
Schmiedeberg subjected cats and dogs to doses of muscarin, large enough to produce death, and when the animals were about to succumb, injected hypodermically from one to two milligrams of sulphate of atropin, after which the toxic symptoms disappeared and the animals completely revived. Prof. Boehm found that digitalin likewise re-established heart action when suspended by the action of muscarin.
In man the fatal termination, in cases of mushroom poisoning, where the antidote is not used, may take place in from 5 to 12 hours or not for two or three days.
According to Prof. E. Kobert's recent chemical analysis, the "Fly mushroom," Amanita muscaria, contains not only the very poisonous alkaloid muscarin and the amanitin of Letellier (cholin), but also a third alkaloid, pilz atropin. The pilz-atropin (mushroom atropin) was discovered by Schmiedeberg in a commercial preparation of muscarin, and later Prof. Kobert discovered it in varying proportions in fresh mushrooms of different species. The effect of this third alkaloid, it is claimed, is to neutralize to a greater or less extent the effect of the poisonous one. Under its influence, when present in quantity, the poison is almost entirely neutralized. Contraction of the pupils changes to dilation, and slowing of the pulse may disappear. Only through the presence of this natural antidote in the Fly mushroom, says Kobert, is it possible, as in some parts of France and Russia, to eat without danger this mushroom, which contains 10% of sugar (trehalose or mycose) in a fermented and unfermented condition. He states also that delirium, intoxication, and other symptoms which, according to Prof. Dittmer of Kamschatka and various scientific travellers, are reported effects of the Fly mushroom in the extreme north, are not experienced in the same degree in southern Russia. This difference in action, he thinks, may be very properly attributed to the varying proportion of the above-mentioned atropin in the mushroom or to the presence of substances which develop only in the extreme north.