Acetylcholine mechanism of action. The mediator acetylcholine and its mechanisms of action. Irreversibly active substances

Are common
Acetylcholine


Systematic name	N,N,N-trimethyl-2-aminoethanol acetate
Abbreviations	ACh
Chemical formula	CH 3 CO 2 CH 2 CH 2 N(CH 3) 3
Empirical formula	C 7 H 16 N O 2
Physical properties
Molar mass	146.21 g/ mole
Thermal properties
Classification
Reg. CAS number	51-84-3
Reg. PubChem number	187
SMILES	O=C(OCC(C)(C)C)C

Properties

Physical

Colorless crystals or white crystalline mass. Dissolves in the air. Easily soluble in water and alcohol. When boiling and long-term storage solutions decompose.

Medical

The peripheral muscarinic-like effect of acetylcholine manifests itself in a slowdown of heart contractions, expansion of peripheral blood vessels and reduction blood pressure, strengthening peristalsis stomach And intestines, contraction of the muscles of the bronchi, uterus, gall and Bladder, strengthening secretion digestive, bronchial, sweat and lacrimal glands, miosis. The miotic effect is associated with increased contraction of the orbicularis iris muscle, which is innervated by postganglionic cholinergic fibers oculomotor nerve. At the same time, as a result of contraction of the ciliary muscle and relaxation of the zonular ligament of the ciliary girdle, spasm accommodation.

Constriction of the pupil caused by the action of acetylcholine is usually accompanied by a decrease intraocular pressure. This effect is partly explained by the fact that when the pupil narrows and the iris flattens, Schlemm's canal (venous sinus of the sclera) and fountain spaces (spaces of the iridocorneal angle) expand, which ensures better outflow of fluid from internal environments eyes. It is possible that other mechanisms are also involved in the decrease in intraocular pressure. Due to their ability to reduce intraocular pressure, substances that act like acetylcholine (cholinomimetics, anticholinesterase drugs) are widely used for treatment glaucoma. It should be borne in mind that when these drugs are introduced into the conjunctival sac, they are absorbed into blood and, having a resorptive effect, can cause symptoms characteristic of these drugs side effects. It should also be borne in mind that long-term (over a number of years) use of miotic substances can sometimes lead to the development of persistent (irreversible) miosis, formation of posterior petechiae and other complications, and long-term use as miotics, anticholinesterase drugs may promote the development cataracts.

Acetylcholine also plays an important role as a neurotransmitter CNS. It is involved in the transmission of impulses in different departments brain, while small concentrations facilitate, and large concentrations inhibit synaptic transmission. Changes in acetylcholine metabolism can lead to impaired brain function. Its deficiency largely determines clinical picture such a dangerous neurodegenerative disease as Alzheimer's disease. Some centrally acting acetylcholine antagonists (see. Amizil) are psychotropic drugs(see also Atropine). Overdose of acetylcholine antagonists may cause disturbances higher nervous activity(have a hallucinogenic effect, etc.).

Application

General Application

For use in medical practice and for experimental research acetylcholine chloride is produced ( lat. Acetylcholini chloridum). How medicine acetylcholine chloride wide application does not have.

Treatment

When taken orally, acetylcholine is ineffective because it is quickly hydrolyzed. At parenteral administration has a quick, sharp, but short-lived effect. Like other quaternary compounds, acetylcholine does not penetrate well blood-brain barrier and does not have a significant impact on CNS. Acetylcholine is sometimes used as vasodilator for spasms peripheral vessels (endarteritis, intermittent claudication, trophic disorders in the stumps, etc.), with arterial spasms retina. In rare cases, acetylcholine is administered for intestinal and bladder atony. Acetylcholine is also sometimes used to facilitate x-ray diagnosis of esophageal achalasia.

Form of application

The drug is prescribed subcutaneously and intramuscularly at a dose (for adults) of 0.05 g or 0.1 g. Injections if necessary, you can repeat 2-3 times a day. When injecting, make sure that the needle does not hit the vein. Intravenous administration not allowed due to the possibility of a sharp decline blood pressure and stops hearts.

Higher doses subcutaneously and intramuscularly for adults:

single dose 0.1 g,
daily 0.3 g.

Danger of use during treatment

When using acetylcholine, it should be taken into account that it causes a narrowing of the coronary vessels of the heart. At overdose may be observed sharp decline blood pressure With bradycardia and violations heart rate, profuse sweat , miosis, increased intestinal motility and other phenomena. In these cases, 1 ml of 0.1% solution should be immediately injected into a vein or under the skin. atropine(repeat if necessary) or another anticholinergic drug (see. Metacin).

Participation in life processes

Acetylcholine formed in the body (endogenous) plays an important role in vital processes: it takes part in the transmission nervous excitement V CNS, autonomic nodes, endings of parasympathetic and motor nerves. Acetylcholine is associated with memory functions. A decrease in acetylcholine in Alzheimer's disease leads to memory impairment in patients. Acetylcholine plays an important role in falling asleep and waking up. Awakening occurs with increased activity cholinergic neurons in basal ganglia of the forebrain And brain stem.

Physiological properties

Acetylcholine is a chemical messenger ( mediator) nervous excitement; graduation nerve fibers, for which it serves as a mediator, are called cholinergic, and the receptors that interact with it are called cholinergic receptors. The cholinergic receptor (according to modern foreign terminology - “cholinergic receptor”) is a complex protein macromolecule(nucleoprotein), localized on outside postsynaptic membrane. In this case, the cholinergic receptor of postganglionic cholinergic nerves (heart, smooth muscles, glands) is designated as m-cholinergic receptors(muscarinic-sensitive), and located in the region of ganglion synapses and in somatic neuromuscular synapses - like n-cholinergic receptors(nicotine sensitive). This division is associated with the characteristics of the reactions that occur during the interaction of acetylcholine with these biochemical systems: muscarinic-like in the first case and nicotine-like in the second; m- and n-cholinergic receptors are also located in different parts CNS.

According to modern data, muscarine-sensitive receptors are divided into M1-, M2- and M3-receptors, which are distributed differently in organs and are heterogeneous in physiological significance(cm. Atropine , Pirenzepin).

Acetylcholine does not have a strict selective effect on the types of cholinergic receptors. To one degree or another, it acts on m- and n-cholinergic receptors and on subgroups of m-cholinergic receptors. The peripheral nicotine-like effect of acetylcholine is associated with its participation in the transmission nerve impulses from preganglionic fibers to postganglionic fibers in the autonomic ganglia, as well as from motor nerves to striated muscles. In small doses it is a physiological transmitter of nervous excitation; in large doses it can cause persistent depolarization in the area of synapses and block the transmission of excitation.

Contraindications

Acetylcholine is contraindicated in bronchial asthma , angina pectoris , atherosclerosis , organic diseases hearts, epilepsy.

Release form

Release form: in 5 ml ampoules containing 0.1 and 0.2 g of dry matter. The drug is dissolved immediately before use. Open the ampoule and inject it into it with a syringe. required amount(2-5 ml) sterile water for

We know very little about the brain and intellectual abilities. However, it is safe to say that one neurotransmitter, acetylcholine, can improve a person's cognitive abilities. According to Darwin's theory, this neurotransmitter should be synthesized more actively with each new generation. Of course, this statement is true if a person does not degrade.

However, today we will not talk about evolution, but will talk about this mediator in more detail, not forgetting to mention ways to increase its concentration. It should be said that increasing acetylcholine levels will not make you happy, but it can speed up the process of learning new information. Simply put, you will learn better.

Acetylcholine: what is it?

The neurotransmitter is responsible not only for intellectual abilities human, but also neuromuscular connections, including autonomic ones. Note that this is one of the first substances of this group that was discovered by scientists, and this happened at the beginning of the last century. It's important to remember that high dosages acetylcholine slows down the body, while small amounts help speed it up. The process of neurotransmitter synthesis is activated when new information is received or old information is reproduced.

The substance is produced by nerve terminals, axons, which represent the junction of two neurons. The synthesis of acetylcholine requires two substances:

Acetyl coenzyme (CoA) - produced from glucose.

Choline - found in some foods.

After this, the neurotransmitter is placed in peculiar containers round shape, called vesicles, and are sent to the presynaptic terminal of the neuron. After the vesicles merge with the cell membrane, acetylcholine is released, entering the synaptic cleft.

Acetylcholine can be retained in the synaptic cleft, penetrate into the next neuron, or be returned back. IN the latter case the neurotransmitter is placed back into the vesicles. Any neurotransmitter strives to connect with its receptors located on the second neuron. Figuratively speaking, the receptor is the door, and the neurotransmitter is the key to it.

IN in this case There are two types of keys, each of which is capable of opening a certain type of “door” - muscarinic and nicotine. For full description process, it is necessary to add that the balance of the substance in the synaptic cleft is monitored by a special enzyme - acetylcholinesterase. If you're in large quantities use nootropics, then after increasing the concentration of acetylcholine to a certain level, this enzyme will begin to work and destroy the excess neurotransmitter into constituent elements.

Alzheimer's disease sharply impairs memory, which is precisely due to excessive activity acetylene esterase. Nowadays, in the treatment of this disease, it is enough good results show drugs that can inhibit the enzyme. However, acetylene esterase inhibitors have one drawback - high concentrations of acetylcholine can be harmful to the body.

Moreover, the side effects can be quite serious, even fatal outcome. Some nerve gases can be classified as acetylene esterase inhibitors. Under their influence, the concentration of the neurotransmitter exceeds permissible limits, which leads to muscle contraction.

Positive effects of acetylcholine and its disadvantages

Let's start with positive effects, which the neurotransmitter we are considering today has:

The cognitive ability of the brain increases and the person becomes smarter.

Memory improves.

The functioning of neuromuscular connections improves - this is extremely useful in sports. Because the body adapts to stress faster.

None narcotic substances cannot increase the level of the neurotransmitter, but will lead to the exact opposite effect - the production of acetylcholine is maximally suppressed by hallucinogens.

Helps you make smart plans, and you will make fewer stupid mistakes due to making impulsive decisions.

This neurotransmitter has only two disadvantages:

Harmful when stressful situation, as it slows down the ability to accept quick solutions.

At high concentrations, it slows down the functioning of the entire body.

However, a small correction needs to be made here - all people are individual, if you have a combination high concentrations acetylcholine and glutamate, you will be faster and more decisive. At the same time, intellectual potential major changes will not endure.

We also note that the neurotransmitter begins to be produced more actively not only when new information is received, but also due to training of the brain and body.

To increase the concentration of the neurotransmitter, you can use the following additives: acetyl l-carnitine, DMAE, lecithin, huperzine, medications for Alzheimer's disease, huperzine. Scopolamine, atropine and diphenhydramine will help reduce the level of the substance. We also recommend that you eat properly so that the concentration of acetylcholine is high and, first of all, pay attention to eggs with nuts.

If you play sports, then acetylcholine will help you achieve better results.

Acetylcholicin is a neurotransmitter that performs binding functions in the human body. This connection carries impulses to the muscles and a number of organs. It is used in research, while its medicinal value currently small due to significant side effects at high dose and the availability of more effective analogues.

General information

Acetylcholine has the formula CH 3 -CO 2 -CH 2 -CH 2 -N(CH 3) 3.

Acetylcholine is organic compound, which acts in the body as, including in the parasympathetic nervous system and in the neuromuscular synapse. As a neurotransmitter, this compound has the following characteristics:

its synthesis occurs in the presynaptic neuron;
accumulation of acetylcholine occurs in the vesicles;
this compound is released in direct proportion to the strength of the stimulus causing such release (impulse frequency);
the postsynoptic action of this substance is directly illustrated by microinophoresis;
This mediator can be deactivated using effective mechanisms.

It has been determined that only compounds that exhibit each of these characteristics can be considered as mediators.

IN chemically Acetylcholine is an ester formed by choline and acetic acid.

In the body, this substance is synthesized through cholinesterase, a special enzyme. When it is destroyed, it forms acetic acid and oxide. The compound is unstable and under the influence of acetylcholinesterase it also disintegrates very quickly.

It's also possible to get it artificially in the form of one or a salt, for example, chloride. The drug obtained in this way (acetylcholine chloride) is used for research in the field of pharmacology and, in rare cases, as medicinal product. The compound is produced in the form of an ampoule with a volume of 5 milliliters, which contains 0.1 or 0.2 grams of dry substance. For injection, it is dissolved in sterile water with a volume of 2–5 milliliters.

Acetylcholine is a crystalline mass white or colorless crystals.

Classification of choline proteins (what they are and their specificity)

Choline proteins are divided into those acting on n-cholinergic receptors and m-cholinergic receptors. Cholinergic receptors are protein macromolecules of complex structure that are located on outside postsynaptic membrane.

The first of them are nichotinosensitive, hence the letter “n” in their name. They are found within neuromuscular structures and ganglion synapses.

The second type of proteins acquired the letter “m” because they are muscarinic-sensitive. They are present in the region of cholinergic postganglionic nerves. In other words, in the heart, smooth muscles and glands.

In the nervous system, acetylcholine is synthesized with the participation of glucose. When it breaks down, acetyl groups appear and energy is released. Thanks to this energy, adenosine triphosphate appears, and through this compound phosphorylation of intermediate compounds required for synthesis occurs. The penultimate stage is the formation of acetyl coenzyme A, from which acetylcholine itself then appears when reacting with choline.

At the same time, the mechanism of cholines entering the site of acetylcholine formation for the reaction with acetyl coenzyme A is currently unknown. It is assumed that half of it comes to this place from the blood plasma, and another half remains after hydrolysis of the previous

The synthesis of this substance occurs in nerve endings inside the cytoplasm of axons. After this, the compound is stored in synaptic vesicles (vesicles). In a separate similar organelle there are from 1000 to 10,000 molecules of this compound. It is assumed that approximately 15–20% of the volume of this substance in the vesicles is the amount of acetylcholine available for immediate use. Other reserves stored in vesicles can be activated for use only some time after the corresponding signal.

The breakdown of acetylcholine in human body happens quite quickly. This process is triggered by acetylcholinesterase, a special enzyme.

Functions

The function of acetylcholine is to serve as a mediator within the CNS (central nervous system). This substance affects the transmission of impulses from one part of the brain to another. At the same time, a small content of this substance promotes the transmission of impulses, and a significant amount of it inhibits it.

Acetylcholine also serves to be transferred to the muscles of the body. With a lack of this substance, the force with which muscles contract decreases. The lack of this particular compound leads to the fact that a person begins to suffer from Alzheimer's disease.

The effect of acetylcholine is expressed in a slower heart rate, decreased blood pressure, increasing the diameter of blood vessels peripheral location. The compound improves peristalsis in digestive tract(intestines and stomach). Also, its presence enhances the contractility of the muscles of a number of organs, including the urinary and gallbladder, uterus, and bronchi. Acetylcholine enhances iron secretion, in particular in the lacrimal, sweat, bronchial and digestive glands.

In addition, it causes constriction of the pupil (miosis), this effect becomes a consequence of more intense contractions of the circular muscle that controls the iris, which is affected by those in oculomotor nerve postganglionic cholinergic fibers. This constriction of the pupil most often occurs in combination with a decrease in intraocular pressure. This is due to the fact that with such a narrowing there is an expansion of Schlemm’s canal, as well as the space in the corner formed by the iris and cornea. As a result, the fluid receives a greater opportunity for outflow from the internal environment of the eye.

Acetylcholine also serves to improve concentration by producing neurons located in.

Another function of the compound is its influence on falling asleep and waking up. The sleeper wakes up after the intensity of the activity of cholinergic neurons located in the brain stem, as well as in forebrain in the basal ganglia.

Acetylcholicin, produced artificially, is used for treatment only in some cases. This is due to the fact that when orally this compound quickly undergoes hydrolysis, resulting in its absorption from the mucous membranes gastrointestinal tract not happening. When introduced into the body in any other way, including through injection, it also does not have a significant effect on the central nervous system. That is why now in most cases they refuse it.

It is also important to keep in mind that acetylcholine constricts the veins in the heart. If an excessive dose of this substance is administered to a patient, the result may be bradycardia, a drop in blood pressure, arrhythmia, sweating and other adverse effects.