Muscarine

Muscarine (Muscarinum)

Muscarine

It is one of the most poisonous alkaloids discovered by Schmiedeberg. It was found in the fly agaric Amanita muscaria or Agaricus Muscarius L. From the subfamily of lamellar fungi of the family Hymenomycetes (Hymenomycetes). Also muscarine was found in mushrooms Boletus luridus and Amanita pantherina and mushroom Inocybe.

Physical properties

This alkaloid obtained from mushrooms is called mushroom or natural muscarine, its empirical formula looks like C5H15NO8, while no structural formula has been found. Natural muscarine is odorless and tasteless and is a syrupy liquid with a strongly alkaline reaction, which, when dried in the presence of sulfuric acid, gradually turns into a crystalline state. In air, alkaloid crystals dissolve very quickly, and muscarineagain turns into a syrupy liquid. It dissolves well in alcohol and water, very poorly in chloroform and does not dissolve at all in ether. If it is heated above 100 degrees, then its destruction occurs, while a not very noticeable smell of tobacco appears. When treated with lead oxide or caustic alkali and heated, it is converted into trimethylamine, and with sulfuric or hydrochloric acid it creates crystalline salts. There is an assumption that the structure of muscarine is similar to that of choline (C5H15NO2):

H3C / CH2CH (OH) 2

H3C - N

H3C / OH

But the experiments of Schmiedeberg and Harnack show that an artificial alkaloid, obtained synthetically from choline, acts differently on animals than a natural one. These experiments showed that artificial and natural muscarines are not identical.

Significance for medicine

Both a natural mushroom alkaloid and a compound obtained synthetically are not currently used for medicinal purposes, but at the same time their medical value is very great. In the old days, attempts were made to treat epilepsy and oncological processes of the glands with muscarin. It was also proposed to use it for eye diseases and for the treatment of ulcers. But all these experiments were stopped due to the exceptional toxicity of the compound.

But muscarine is of great toxic, theoretical and pharmacological significance. It belongs to the parasympathicotropic group of poisons, which have an exciting effect on the peripheral parasympathicotropic nerves, while the alkaloid strictly selectively acts on the nervous system. This feature gives it great value as a pharmacological agent that can be used in experiments like electrical stimulation or instead of it.

If, in small doses, natural muscarine is introduced into the animal's body, then cardiac activity slows down (negative inotropic and chronotropic action), and in large doses it first causes a slowdown and weakening of systolic contractions. And then in the diastolic phase, there is a complete cardiac arrest.

Action on the body

Studies by various scientists show that muscarine has a paralyzing effect on the peripheral nervous system of the respiratory tract, causes an increased contraction of the muscles of the stomach and intestines, and the movement of the intestines is visible even through the lining of the abdominal wall. If muscarine is injected in a large dose, it causes erratic peristaltic movements, which are replaced by antiperistalsis, vomiting and diarrhea begin. A clear sign of muscarine poisoning is the spastic nature of the contractions of the entire stomach or its individual sections, followed by relaxation. According to Schmiedeberg, muscarine has a very strong effect on the intestines and stomach, not only due to its effect on the endings of the vagus nerves, which are located in these organs, but also due to the effect on the cells of the Auerbach plexus ganglion.This alkaloid also causes spastic contractions in other smooth muscle organs such as the uterus, spleen, and bladder. The contraction occurs as a result of the irritating effect of the substance on the peripheral receptors of the parasympathetic nerves located in these organs, as well as as a result of the effect on automatic nerve ganglion devices, by analogy with how it happens in the heart. The pupil of the eye under the influence of muscarin is greatly narrowed, and a spasm of accommodation develops. These two phenomena are due to the action of the alkaloid on the receptors of the parasympathetic fibers of the oculomotor nerve, which are located in the circular nerves of the iris and in the ciliary muscle.The contraction occurs as a result of the irritating effect of the substance on the peripheral receptors of the parasympathetic nerves located in these organs, as well as as a result of the effect on automatic nerve ganglion devices, by analogy with how it happens in the heart. The pupil of the eye under the influence of muscarin is greatly narrowed, and a spasm of accommodation develops. These two phenomena are due to the action of the alkaloid on the receptors of the parasympathetic fibers of the oculomotor nerve, which are located in the circular nerves of the iris and in the ciliary muscle.The contraction occurs as a result of the irritating effect of the substance on the peripheral receptors of the parasympathetic nerves located in these organs, as well as as a result of the effect on automatic nerve ganglion devices, by analogy with how it happens in the heart. The pupil of the eye under the influence of muscarin is greatly narrowed, and a spasm of accommodation develops. These two phenomena are due to the action of the alkaloid on the receptors of the parasympathetic fibers of the oculomotor nerve, which are located in the circular nerves of the iris and in the ciliary muscle.These two phenomena are due to the action of the alkaloid on the receptors of the parasympathetic fibers of the oculomotor nerve, which are located in the circular nerves of the iris and in the ciliary muscle.These two phenomena are due to the action of the alkaloid on the receptors of the parasympathetic fibers of the oculomotor nerve, which are located in the circular nerves of the iris and in the ciliary muscle.

Schmiedeberg found that mushroom muscarine does not act on motor nerves, in contrast to artificial, which paralyzes motor nerve endings. This was later confirmed by Hans Meyer and Gonda. Thus, only synthetic muscarine derived from choline has curariform properties.

Mushroom muscarine activates the glands of the gastrointestinal tract, stimulates the secretion of bile and pancreatic juice. It also increases salivation, sweating and tearing. The secretion of saliva under the action of muscarin is explained by the fact that it irritates peripheral nerve endings (this was proved by Schmiedeberg). The secretion of all other glands is enhanced by the irritating action of muscarin on their separating nerves. In this case, peripheral nerve endings are the target of muscarinic action.

The direct antagonist of muscarin is atropine, which blocks the effect of muscarin by paralyzing the endings of the parasympathetic nerves. This occurs when muscarine has an irritating effect on the peripheral receptors of any of the parasympathetic nerves. Therefore, atropine quickly eliminates diastolic cardiac arrest and slowing heart rate triggered by muscarine. Also, atropine stops increased peristalsis, antiperistalsis and spasms of the stomach and intestines, spasm of accommodation and contraction of the pupil, contraction of the bladder, as well as enhanced secretory function of various glands (sweat, salivary and others). Atropine sulfate has its antagonistic effect on muscarin in a sufficiently small amount (0.001-0.1 mg). It is also knownthat muscarine stops the action of atropine on the frog's heart, eyes, submandibular gland and sweat glands. Therefore, there is an opinion that muscarine and atropine are mutual antagonists. But at the same time, a lot of muscarine is required (up to 7 g) in order for the effect of atropine to stop. In this regard, it is hardly appropriate to say that muscarine has a specific effect relative to atropine, and many pharmacologists are of the opinion that the question of the bilateral antagonism of these two compounds has not yet been resolved.that muscarine has a specific effect on atropine, and many pharmacologists are of the opinion that the question of the bilateral antagonism of these two compounds has not yet been resolved.that muscarine has a specific effect on atropine, and many pharmacologists are of the opinion that the question of the bilateral antagonism of these two compounds has not yet been resolved.

Also antagonists of muscarine include aconitine, hyoscyamine, veratrin, scopolamine, physostigmine, digitalin, dolphin, camphor, gelleborine, chloral hydrate, adrenaline. There are interesting facts outlined by Zondek that calcium chloride also has an antagonistic effect on muscarine.

The sensitivity of different animals to muscarine can vary greatly. So the cat dies from subcutaneous injection of muscarine at a dose of 4 mg after a few hours, and at a dose of 12 mg after 10-15 minutes. Dogs tolerate higher doses of the alkaloid. People have a very high sensitivity to this substance. Schmiedeberg and Koppé conducted experiments on themselves and found that the injection of muscarine at a dose of 3 mg already causes poisoning, which is manifested by very strong salivation, rush of blood to the head, dizziness, weakness, reddening of the skin, nausea and sharp abdominal pain, tachycardia, disorder vision and spasm of accommodation. There is also increased sweating on the face and slightly less on other parts of the body.

Poisoning pattern

In case of mushroom poisoning, the picture may be similar to the description of muscarine poisoning, but usually it still differs due to the fact that fly agarics contain various poisonous atropine-like substances and other compounds that, on the one hand, affect the central nervous system, and on the other hand, stop the action of muscarine ... Therefore, poisoning can be characterized by either symptoms from the stomach and intestines (nausea, vomiting, pain, diarrhea) or completely other symptoms, for example, a state of intoxication, accompanied by delirium and strong agitation, dizziness, an irrepressible desire to destroy everything around, the need for movement. Then there is a tremor throughout the body, epileptiform and tetanic convulsions occur, the pupil expands, the rapid pulse becomes much less frequent, breathing is disturbed, it becomes irregular,body temperature drops sharply and a state of collapse develops. In this condition, death occurs in two to three days. In case of recovery, a person recovers very slowly, a state of hyperleukocytosis is observed in the blood, and the blood itself coagulates very poorly. But today there is no reliable and fully confirmed data on changes in blood, just as there is no data on pathological changes in case of poisoning.

First aid

First of all, in case of mushroom poisoning, you need to remove the contents from the stomach and intestines. To do this, use emetics, gastric lavage with a probe, and the intestines with an enema. Inside, castor oil is drunk in large doses. If symptoms of poisoning, characteristic of muscarin, prevail, then atropine is injected subcutaneously. If the poisoning develops mainly under the influence of atropine-like substances, then atropine cannot be used as an antidote.

Artificial muscarine, which is derived from choline, is the most studied. Very little is known about other artificial muscarines. Anhydromuscarin increases the secretion of sweat and saliva and does not affect the eyes and heart in any way. It causes death due to respiratory paralysis. Isomuscarin does not cause cardiac arrest, but it slows the heart rate, which can be eliminated by atropine. In birds, it leads to a contraction of the pupil, and in mammals it has a curariform effect on the motor nerves and enhances the secretory function of the glands, does not affect the eyes and intestines, but instead increases blood pressure. Ptomatomuscarin has a similar effect to choline muscarin, which suggests that they have a similar chemical structure. The pharmacological action of uromuscarins has not yet been studied.The same can be said about the pharmacological action of carnomuscarin.