home Audience 5 What is acetylcholine? The effect of acetylcholine. Acetylcholine is a neurotransmitter. Acetylcholine: features, drugs, properties

What is acetylcholine? The effect of acetylcholine. Acetylcholine is a neurotransmitter. Acetylcholine: features, drugs, properties

Gross formula

C 7 H 16 ClNO 2

Pharmacological group of the substance Acetylcholine

Nosological classification (ICD-10)

CAS code

60-31-1

Characteristics of the substance Acetylcholine

Acetylcholine chloride - colorless crystals or white crystalline mass. Spreads out in the air. Easily soluble in water, chloroform and ethanol; practically insoluble in ether.

Pharmacology

pharmachologic effect- cholinomimetic.

Carries out the transmission of nerve impulses in the central nervous system, autonomic ganglia, endings of parasympathetic and motor nerves, excites postsynaptic membranes sweat glands. Interacts with m- and n-cholinergic receptors, causes membrane depolarization, increases the permeability for sodium ions, equalizing the voltage potential. Stimulation of m-cholinergic receptors increases the content of "secondary mediators" (cAMP and cGMP). The local synaptic potential generates an action potential in the neuron of the next stage or increases the functional activity of organ cells (muscles, glands, etc.).

With systemic action, m-cholinomimetic effects predominate: bradycardia, expansion blood vessels, lowering blood pressure, increasing the tone and contractility of the smooth muscles of the bronchi, gastrointestinal tract, uterus, bile and Bladder, increased secretion of digestive, bronchial, sweat and lacrimal glands, pupillary constriction (miosis), spasm of accommodation. Reduces intraocular pressure(with narrowing of the pupil and flattening of the iris, the Schlemm canal and spaces of the iridocorneal angle expand, the outflow improves intraocular fluid). The stimulating effect on the n-cholinergic receptors of the autonomic ganglia (sympathetic and parasympathetic) is significantly manifested only with the blockade of the m-cholinergic receptors.

When taken orally, it is ineffective, because. easily hydrolyzed; under conditions of parenteral administration, it has a quick, but short-term effect. After application into the conjunctival sac, it is absorbed into the blood, has a resorptive effect. Poorly penetrates through the BBB.

Application of the substance Acetylcholine

Operations on the anterior chamber of the eye (cataract removal, keratoplasty, iridectomy) - to ensure miosis within a few seconds after the release of the lens; spasm of the retinal arteries; rarely - endarteritis, intermittent claudication, trophic disorders in the stumps, atony of the intestines and bladder, radiodiagnosis of esophageal achalasia.

Contraindications

Hypersensitivity, bronchial asthma, chronic heart failure stage II-III, angina pectoris, atherosclerosis, epilepsy, bleeding from the gastrointestinal tract.

Use during pregnancy and lactation

Side effects of acetylcholine

With systemic use or systemic absorption: narrowing coronary vessels, bradycardia, arrhythmia, lowering blood pressure, redness of the face, difficulty breathing, increased sweating.

When applied to the eyes: swelling, clouding of the cornea.

Interaction

It shows antagonism with adrenomimetics in terms of its effect on the size of the pupil. Beta-blockers, anticholinesterase drugs, adrenomimetics increase the antiglaucoma effect. Tricyclic antidepressants, m-anticholinergics, phenothiazine, chlorprothixene, clozapine reduce parasympathetic activity. Halothane enhances side effects. When combined with quinidine, ventricular flutter is possible. In / in the introduction is not allowed (possibly a sharp decrease in blood pressure and cardiac arrest).

Long-term application (for several years) to the conjunctival sac can lead to irreversible miosis and the formation of posterior petechiae.

For prolongation of miosis, preliminary instillation of pilocarpine is possible. In cataract surgery, it is used only after the lens has been isolated.

Mechanism of action of acetylcholine

Cholinergic receptors (acetylcholine receptors) are transmembrane receptors, the ligand of which is acetylcholine.

Acetylcholine serves as a neurotransmitter at both pre- and postganglionic synapses. parasympathetic system and in preganglionic sympathetic synapses, in a number of postganglionic sympathetic synapses, neuromuscular synapses (somatic nervous system), and also in some parts of the central nervous system. Nerve fibers that release acetylcholine from their endings are called cholinergic.

Synthesis of acetylcholine occurs in the cytoplasm of nerve endings; its reserves are stored in the form of vesicles in presynaptic terminals. The occurrence of a presynaptic action potential leads to the release of the contents of several hundred vesicles into the synaptic cleft. Acetylcholine released from these vesicles binds to specific receptors on the postsynaptic membrane, which increases its permeability to sodium, potassium and calcium ions and leads to the appearance of an excitatory postsynaptic potential. The action of acetylcholine is limited by its hydrolysis by the enzyme acetylcholinesterase.

Specific cholinergic receptors from a pharmacological point of view are divided into nicotinic (H-receptors) and muscarinic (M-receptors).

The acetylcholine nicotinic receptor is also an ion channel; refers to channeloformer receptors, while the acetylcholine muscarinic receptor belongs to the class of serpentine receptors that transmit signal through heterotrimeric G proteins.

Cholinergic receptors of autonomic ganglia and internal organs differ.

N-cholinergic receptors (sensitive to nicotine) are located on postganglionic neurons and cells of the adrenal medulla, and on internal organs- M-cholinergic receptors (sensitive to the alkaloid muscarine). The former are blocked by ganglioblockers, the latter by atropine.

M-cholinergic receptors are divided into several subtypes:

M1-cholinergic receptors are located in the central nervous system and, possibly, on neurons of parasympathetic ganglia;

M2-cholinergic receptors - on smooth and cardiac muscles and cells of the glandular epithelium.

M3-cholinergic receptors are located on smooth muscles and glands.

Bethanechol serves as a selective stimulator of M2-cholinergic receptors. An example of a selective blocker of M1-cholinergic receptors is pirenzepine. This drug dramatically suppresses the production of HCl in the stomach.

Stimulation of M2-cholinergic receptors through Gi-protein leads to inhibition of adenylate cyclase, and stimulation of M2-cholinergic receptors through Gq-protein leads to activation of phospholipase C and the formation of IP3 and DAG (Fig. 70.5).

Stimulation of M3-cholinergic receptors also leads to the activation of phospholipase C. Atropine serves as a blocker of these receptors.

Other subtypes of M-cholinergic receptors have also been identified by molecular biology methods, but they have not yet been sufficiently studied.

Acetylcholine (acetylcholine, Ach) [lat. acetum - vinegar, Greek. chole - bile and lat. -in(e) - suffix denoting "similar"] - acetic ester of choline (see Choline), a neurotransmitter that transmits nervous excitation through the synaptic cleft in the parasympathetic nervous system; synthesized in tissues with the participation of choline acetylase, hydrolyzed by the enzyme acetylcholinesterase. A. is also found in some plant poisons. First isolated from ergot in 1914 by G. Dale. For establishing the role of A. in the transmission of a nerve impulse, he, together with O. Levy, received Nobel Prize for 1936

Acetylcholine acts through cholinergic nerve endings, myoneural end plates and other cholinergic receptors. Being in the protein-lipoid complex (precursor), acetylcholine is released during electrical and nervous excitation. Palay's research in 1956, using electron microscopy, showed the accumulation of liquid drops in the pores of the synapse, some of which burst during the passage of a nerve impulse. It is believed that the secreted fluid is acetylcholine (pinocytosis theory). Being released in the cholinergic substances of the heart, acetylcholine acts on adjacent cell membranes. According to modern views, the membrane carries a certain electric charge, due to the redistribution of the K ion. The concentration of potassium at rest is much higher inside the cell than outside. For sodium, on the contrary, the concentration outside the cell is large, and inside it is small. The concentration of sodium ions inside the cell remains constant due to its active removal from the cell during a process called the "sodium pump". Potassium, on the other hand, penetrates the cell surface, leaving a more massive anion inside it, so the outer surface of the cell receives an excess of positive charges, while the inner one receives negative ones. The more potassium cations leave the cell, the higher the charge of its membrane turns out to be, and vice versa - when the release of potassium slows down, the membrane potential decreases. Direct measurements of the resting potential showed that it is approximately 90 mV in the myocardium of the ventricles and atria, and 70 mV in the sinus node. If, for any reason, the membrane potential drops to 50 mV, the properties of the membrane change dramatically and it passes a significant amount of sodium ions into the cell. Then positive ions prevail inside the cell and membrane potential changes its sign. Recharging (depolarization) of the membrane causes an electrical action potential. After the contraction, the concentrations of potassium and sodium characteristic of the resting state (repolarization) are restored.

It has been established that cholinergic (parasympathomimetic, parasympathotropic, trophotropic) reactions occur when acetylcholine (or other choline compounds) act on cholinergic receptors, subcellular formations, cells, tissues, organs or the body as a whole. In addition to its main (cholinergic) action, acetylcholine causes the release of potassium bound by proteins, increases or decreases the permeability of biological membranes, takes part in the regulation of the selective permeability of erythrocytes, changes the activity of individual respiratory enzymes, affects the activity of cathepsins, the renewal of the phosphate group in phospholipids, metabolism of macroergic phosphorus compounds, increases the resistance of individual tissues and the body as a whole to hypoxia. Koshtoyants suggested that, by carrying out a mediator action, acetylcholine enters the circle of tissue biochemical transformations.

The normal mechanism of automatism in the heart is based on a spontaneous decrease in potential sinus node up to -50 mV (generator potential). This occurs in the sinus node through a specific metabolic process based on a decrease in membrane permeability to potassium. Acetylcholine, on the contrary, specifically increases the permeability to the membrane of the sinus node, thereby increasing the output of K and preventing the development of the generator potential. Therefore, the heart rate drops. If the concentration of acetylcholine is increased even more, then the generator potential develops so slowly that the membranes of the sinus node lose their ability to develop an action potential (accommodation of the membrane). There is a cardiac arrest. An increase in potassium permeability under the influence of acetylcholine causes a faster process of restoring the membrane's resting potential (repolarization). The injected acetylcholine is not always distributed uniformly in the blood. Therefore, in the atrium, this process of accelerated repolarization can also go unevenly, which, with the remaining excitation of the sinus node, manifests itself as flutter and atrial fibrillation. The ventricles of the heart, devoid of cholinergic endings, remain insensitive to acetylcholine. The activation of centers of automatism of the second order (His bundle) is associated with the property of Purkinje fibers to develop spontaneous depolarization in the same way as it occurs in the sinus node.

The non-mediator action of acetylcholine in the whole organism is one of the least studied and most controversial sections of the humoral-hormonal regulation of functions. It has been established that cholinergic (parasympathomimetic, parasympathotropic, trophotropic) reactions occur under the action of acetylcholine (or other choline compounds) on cholinergic receptors, subcellular formations, cells, tissues, organs or the body as a whole. In addition to its main (cholinergic) action, acetylcholine causes the release of potassium bound by proteins, increases or decreases the permeability of biological membranes, takes part in the regulation of the selective permeability of erythrocytes, changes the activity of individual respiratory enzymes, affects the activity of cathepsins, the renewal of the phosphate group in phospholipids, metabolism of high-energy phosphorus compounds, increases the resistance of individual tissues and the body as a whole to hypoxia. Koshtoyants suggested that, by carrying out a mediator action, acetylcholine enters the circle of tissue biochemical transformations. And the inhibition of the action of acetylcholine is to some extent functionally equivalent to an increase in the concentration of dopamine.

Biochemical effect acetylcholine is that its attachment to the receptor opens a channel for the passage of Na and K ions through the cell membrane, which leads to membrane depolarization. Blocking the action of acetylcholine is fraught with serious problems, up to fatality. This is the biochemical action of neurotoxins. The structures of two of the most potent neurotoxins, histrionicotoxin and D-tubocurarine chloride, are shown below. Like acetylcholine, the D-tubocurarine molecule contains ammonium moieties. It blocks the site of attachment of acetylcholine to the receptor, excludes the transmission of a nerve signal, and prevents the transfer of ions through the membrane. A situation called paralysis of the living system is created.

The effect of acetylcholine on the heart.

cholinergic mechanisms. On the outer membrane of cardiomyocytes, mainly muscarinic-sensitive (M-) cholinergic receptors are presented. The presence of nicotine-sensitive (N-) cholinergic receptors in the myocardium has also been proven, but their significance in parasympathetic influences on the heart is less clear. The density of muscarinic receptors in the myocardium depends on the concentration of muscarinic agonists in the tissue fluid. Excitation of muscarinic receptors inhibits the activity of the pacemaker cells of the sinus node and at the same time increases the excitability of atrial cardiomyocytes. These two processes can lead to the occurrence of atrial extrasystoles in the event of an increase in tone. vagus nerve e.g. at night while sleeping. Thus, the excitation of M-cholinergic receptors causes a decrease in the frequency and strength of atrial contractions, but increases their excitability.

Acetylcholine inhibits conduction in the atrioventricular node. This is due to the fact that under the influence of acetylcholine, hyperpolarization of the cells of the atrioventricular node occurs due to an increase in the outgoing potassium current. Thus, excitation of muscarinic cholinergic receptors has the opposite effect on the heart compared to activation of B-adrenergic receptors. At the same time, the heart rate decreases, the conductivity and contractility of the myocardium is inhibited, as well as the consumption of oxygen by the myocardium. The excitability of the atria in response to the use of acetylcholine increases, while the excitability of the ventricles, on the contrary, decreases.

Acetylcholine is one of the most important neurotransmitters in the brain. Acetylcholine's most prominent role is in neuromuscular transmission, where it is an excitatory transmitter. It is known that acetylcholine can have both excitatory and inhibitory effects. This depends on the nature of the ion channel, which it regulates when interacting with the corresponding receptor.

The neurotransmitter acetylcholine is released from vesicles in presynaptic nerve terminals and binds to both nicotinic receptors and muscarinic receptors on the cell surface. These two types of acetycholine receptors differ significantly in both structure and function.

Acetylcholine - choline acetate ester, is a mediator in neuromuscular junctions, in presynaptic endings of motor neurons on Renshaw cells, in sympathetic department vegetative nervous system- in all ganglionic synapses, in the synapses of the adrenal medulla and in the postganglionic synapses of the sweat glands; in the parasympathetic division of the autonomic nervous system - also in the synapses of all ganglia and in the postganglionic synapses of the effector organs. In the CNS, acetylcholine was found in fractions of many parts of the brain, sometimes in significant amounts, but no central cholinergic synapses could be found.

Acetylcholine is synthesized in nerve endings from choline, which comes there with the help of an unknown transport mechanism. Half of the incoming choline is formed as a result of the hydrolysis of previously released acetylcholine, and the rest, apparently, comes from the blood plasma. The enzyme choline acetyltransferase is formed in the soma of the neuron and transported along the axon to the presynaptic nerve endings in about 10 days. The mechanism by which synthesized acetylcholine enters synaptic vesicles is still unknown.

Apparently, only a small part (15-20%) of the stock of acetylcholine, which is stored in the vesicles, is the fraction of the immediately available mediator, ready to be released - spontaneously or under the influence of an action potential.

The deposited fraction can be mobilized only after some delay. This is confirmed, firstly, by the fact that the newly synthesized acetylcholine is released about twice as fast as the previously present one, and secondly, at non-physiologically high stimulation frequencies, the amount of acetylcholine released in response to one impulse drops to such a level at which the amount of acetylcholine released during each minute remains constant. After blockade of choline uptake by hemicholinium, not all acetylcholine is released from the nerve endings. Therefore, there must be a third, stationary fraction, which may not be enclosed in synaptic vesicles. Apparently, there can be an exchange between these three factions. The histological correlates of these fractions have not yet been elucidated, but it is assumed that the vesicles located near the synaptic cleft constitute the fraction of the immediately available mediator, while the remaining vesicles correspond to the deposited fraction or part of it.

On the postsynaptic membrane, acetylcholine binds to specific macromolecules called receptors. These receptors are probably a lipoprotein with a molecular weight of about 300,000. Acetylcholine receptors are located only on outer surface postsynaptic membrane and are absent in neighboring postsynaptic areas. Their density is about 10,000 per 1 sq. µm.

Acetylcholine serves as a mediator of all preganglionic neurons, postganglionic parasympathetic neurons, postganglionic sympathetic neurons innervating merocrine sweat glands, and somatic nerves. It is formed in nerve endings from acetyl-CoA and choline by the action of choline acetyltransferase. In turn, choline is actively captured by presynaptic endings from the extracellular fluid. In nerve endings, acetylcholine is stored in synaptic vesicles and released in response to an action potential and the entry of divalent calcium ions. Acetylcholine is one of the most important neurotransmitters in the brain.

If the end plate is exposed to acetylcholine for a few hundred milliseconds, the initially depolarized membrane gradually repolarizes despite the constant presence of acetylcholine, i.e. postsynaptic receptors are inactivated. The causes and mechanism of this process have not yet been studied.

Usually, the action of acetylcholine on the postsynaptic membrane lasts only 1-2 ms, because part of the acetylcholine diffuses from the end plate region, and part is hydrolyzed by the enzyme acetylcholinesterase (i.e., it is split into ineffective components choline and acetic acid). Acetylcholinesterase in large quantities is present in the end plate (the so-called specific or true cholinesterase), however, cholinesterases are also found in erythrocytes (also specific) and in blood plasma (non-specific, i.e. they also break down other choline esters). Therefore, acetylcholine, which diffuses from the end plate region into the surrounding intercellular space and enters the bloodstream, is also split into choline and acetic acid. Most of choline from the blood again enters the presynaptic endings.

The action of acetylcholine on the postsynaptic membrane of postganglionic neurons can be reproduced by nicotine, and on the effector organs by muscarine (fly agaric toxin). In this regard, a hypothesis arose about the presence of two types of macromolecular acetylcholine receptors, and its effect on these receptors is called nicotine-like or muscarine-like. The nicotine-like action is blocked by bases, and the muscarine-like action is blocked by atropine.

Substances that act on the cells of effector organs in the same way as cholinergic postganglionic parasympathetic neurons are called parasympathomimetic, and substances that weaken the action of acetylcholine are called parasympatholytic.

Bibliography

cholinergic receptor acetylcholine neuron

1. Kharkevich D.A. Pharmacology. M.: GEOTAR-MED, 2004

2. Zeimal E.V., Shelkovnikov S.A. - Muscarinic cholinergic receptors

3. Sergeev P.V., Galenko-Yaroshevsky P.A., Shimanovsky N.L., Essays on biochemical pharmacology, M., 1996.

4. Hugo F. Neurochemistry, M, Mir, 1990

5. Sergeev P.V., Shimanovsky N.L., V.I. Petrov, Receptors, Moscow - Volgograd, 1999

It plays an important role in processes such as memory and learning.




Are common
Systematic Name	N,N,N-trimethyl-2-aminoethanol acetate
Abbreviations	ACH
Chem. formula	CH 3 CO (O) CH 2 CH 2 N (CH 3) 3
Physical properties
Molar mass	146.21 g/mol
Classification
Reg. CAS number	51-84-3
PubChem
Reg. EINECS number	200-128-9
SMILES
InChI
Codex Alimentarius	E1001(i)
CHEBI	And
ChemSpider
Data is based on standard conditions (25 °C, 100 kPa) unless otherwise noted.

Properties

Physical

Colorless crystals or white crystalline mass. Spreads out in the air. Easily soluble in water and alcohol. When boiled and stored for a long time, the solutions decompose.

Medical

The physiological cholinomimetic effect of acetylcholine is due to its stimulation of the terminal membranes of m- and n-cholinergic receptors.

Peripheral muscarine-like action of acetylcholine is manifested in slowing heart rate, expanding peripheral blood vessels and lowering blood pressure, increased peristalsis of the stomach and intestines, contraction of the muscles of the bronchi, uterus, gallbladder and bladder, increased secretion of the digestive, bronchial, sweat and lacrimal glands, miosis. The myotic effect is associated with increased contraction of the circular muscle of the iris, which is innervated by postganglionic cholinergic fibers of the oculomotor nerve. At the same time, as a result of contraction of the ciliary muscle and relaxation of the zinn ligament of the ciliary girdle, an accommodation spasm occurs.

The constriction of the pupil, due to the action of acetylcholine, is usually accompanied by a decrease in intraocular pressure. This effect is partly explained by the fact that with the narrowing of the pupil and flattening of the iris, the canal of Schlemm (the venous sinus of the sclera) and the fountain spaces (spaces of the iriocorneal angle) expand, which provides a better outflow of fluid from the internal media of the eye. It is possible that other mechanisms are involved in lowering intraocular pressure. In connection with the ability to reduce intraocular pressure, substances that act like acetylcholine (cholinomimetics, anticholinesterase drugs) are widely used for the treatment of glaucoma. It should be borne in mind that when these drugs are introduced into the conjunctival sac, they are absorbed into the blood and, having a resorptive effect, can cause side effects. It should also be borne in mind that long-term (over a number of years) use of myotic substances can sometimes lead to the development of persistent (irreversible) miosis, the formation of posterior synechia and other complications, and long-term use as miotics, anticholinesterase drugs may contribute to the development of cataracts.

Acetylcholine also plays an important role as a CNS mediator. It is involved in the transmission of impulses in different parts of the brain, while small concentrations facilitate, and large ones inhibit synaptic transmission. Changes in the metabolism of acetylcholine lead to gross violation brain functions. 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). An overdose of acetylcholine antagonists can cause disturbances in higher nervous activity (have a hallucinogenic effect, etc.). The anticholinesterase action of a number of poisons is based precisely on the ability to cause the accumulation of acetylcholine in synaptic clefts, overexcitation of cholinergic systems and more or less rapid death (chlorophos, karbofos, sarin, soman) (Burnazyan, "Toxicology for medical students", Kharkevich D.I., " Pharmacology for students of the Faculty of Medicine).

Application

General application

For use in medical practice and for experimental studies, acetylcholine chloride is produced (lat. Acetylcholini chloridum). As a drug acetylcholine chloride wide application does not have.

Treatment

When taken orally, acetylcholine hydrolyzes very quickly and is not absorbed from the mucous membranes of the gastrointestinal tract. When administered parenterally, it has a quick, sharp and short-lived effect (like adrenaline). Like other quaternary compounds, acetylcholine does not penetrate well from the vascular bed through the blood-brain barrier and does not have a significant effect on the central nervous system when administered intravenously. Sometimes in the experiment, acetylcholine is used as a vasodilator for spasms of peripheral vessels (endarteritis, intermittent claudication, trophic disorders in the stumps, etc.), with spasms of the retinal arteries. IN rare cases acetylcholine was administered for atony of the intestines and bladder. Acetylcholine has also been used occasionally to relieve X-ray diagnostics achalasia of the esophagus.

Form of application

Since the 1980s, acetylcholine has not been used as a drug in practical medicine (M. D. Mashkovsky, "Drugs", Volume 1), since there is a large number of synthetic cholinomimetics with a longer and more targeted action. It was administered under the skin and intramuscularly at a dose (for adults) of 0.05 g or 0.1 g. Injections, if necessary, were repeated 2-3 times a day. When injecting, it was necessary to make sure that the needle did not enter the vein. Intravenous administration cholinomimetics are not allowed due to the possibility of a sharp decrease in blood pressure and cardiac arrest.

Danger of use in treatment

When using acetylcholine, it should be borne in mind that it causes constriction of the coronary vessels of the heart. In case of an overdose, a sharp decrease in blood pressure with bradycardia and cardiac arrhythmias, profuse sweat, miosis, increased intestinal motility and other phenomena can be observed. In these cases, you should immediately enter into a vein or under the skin 1 ml of a 0.1% solution of atropine (repeated if necessary) or another anticholinergic drug (see Metacin).

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/mol
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. Spreads out in the air. Easily soluble in water and alcohol. When boiled and stored for a long time, the solutions decompose.

Medical

Peripheral muscarine-like action of acetylcholine is manifested in slowing heart rate, expanding peripheral blood vessels and lowering blood pressure, increased peristalsis of the stomach and intestines, contraction of the muscles of the bronchi, uterus, gall bladder and bladder, increased secretion of the digestive, bronchial, sweat and lacrimal glands, miosis. The myotic effect is associated with increased contraction of the circular muscle of the iris, which is innervated by postganglionic cholinergic fibers of the oculomotor nerve. At the same time, as a result of the contraction of the ciliary muscle and the relaxation of the ligament of the ciliary girdle, a spasm of accommodation occurs.

The constriction of the pupil, due to the action of acetylcholine, is usually accompanied by a decrease in intraocular pressure. This effect is partly due to the fact that when the pupil is constricted and the iris is flattened, the canal of Schlemm expands ( venous sinus sclera) and fountain spaces (spaces of the iridocorneal angle), which provides a better outflow of fluid from the internal media of the eye. It is possible that other mechanisms are involved in lowering intraocular pressure. In connection with the ability to reduce intraocular pressure, substances that act like acetylcholine (cholinomimetics, anticholinesterase drugs) are widely used for the treatment of glaucoma. It should be borne in mind that when these drugs are introduced into the conjunctival sac, they are absorbed into the blood and, having a resorptive effect, can cause side effects characteristic of these drugs. 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, the formation of posterior petechiae and other complications, and long-term use of anticholinesterase drugs as miotics can contribute to the development of cataracts.

Application

General application

For use in medical practice and for experimental studies, acetylcholine chloride (lat. Acetylcholini chloridum). As a drug, acetylcholine chloride is not widely used.

Treatment

When taken orally, acetylcholine is ineffective, as it is rapidly hydrolyzed. When administered parenterally, it has a quick, sharp, but short-lived effect. Like other quaternary compounds, acetylcholine does not penetrate the blood-brain barrier well and does not significantly affect the CNS. Sometimes acetylcholine is used as a vasodilator for spasms of peripheral vessels (endarteritis, intermittent claudication, trophic disorders in the stumps, etc.), with spasms of the retinal arteries. In rare cases, acetylcholine is administered with atony of the intestines and bladder. Acetylcholine is also sometimes used to facilitate the radiological diagnosis of esophageal achalasia.

Form of application

The drug is prescribed under the skin and intramuscularly at a dose (for adults) of 0.05 g or 0.1 g. Injections, if necessary, can be repeated 2-3 times a day. When injecting, make sure that the needle does not enter a vein. Intravenous administration is not allowed due to the possibility of a sharp decrease in blood pressure and cardiac arrest.

Higher doses under the skin and intramuscularly for adults:

single 0.1 g,
daily 0.3 g.

Danger of use in treatment

Participation in life processes

Formed in the body (endogenous) acetylcholine plays a role important role in life processes: it takes part in the transmission nervous excitement in the central nervous system, autonomic nodes, endings of parasympathetic and motor nerves. Acetylcholine is associated with memory functions. A decrease in acetylcholine in Alzheimer's disease leads to a weakening of memory in patients. Acetylcholine plays an important role in falling asleep and waking up. Awakening occurs with increased activity of cholinergic neurons in the basal forebrain nuclei and the brainstem.

Physiological properties

Acetylcholine is a chemical transmitter (mediator) of nervous excitation; the endings of the nerve fibers for which it serves as a mediator are called cholinergic, and the receptors that interact with it are called cholinergic receptors. Cholinergic receptor (according to modern foreign terminology - "cholinergic receptor") is a complex protein macromolecule (nucleoprotein) localized on outside postsynaptic membrane. At the same time, the cholinergic receptor of postganglionic cholinergic nerves (heart, smooth muscles, glands) is designated as m-cholinergic receptors (muscarinic-sensitive), and those located in the region of ganglionic synapses and in somatic neuromuscular synapses - as n-cholinergic receptors (nicotine-sensitive). This division is associated with the peculiarities of the reactions that occur during the interaction of acetylcholine with these biochemical systems: muscarine-like in the first case and nicotine-like in the second; m- and n-cholinergic receptors are also located in different parts of the central nervous system.

According to modern data, muscarinic receptors are divided into M1-, M2- and M3-receptors, which are distributed differently in organs and are heterogeneous in physiological significance(see Atropine, Pirenzepine).

Acetylcholine does not have a strict selective effect on the varieties 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 of nerve impulses from preganglionic fibers to postganglionic fibers in the autonomic nodes, as well as from motor nerves to striated muscles. In small doses, it is a physiological transmitter of nervous excitation, in large doses can cause persistent depolarization in the area of synapses and block the transmission of excitation.

Contraindications

Acetylcholine is contraindicated in bronchial asthma, angina, atherosclerosis, organic heart disease, epilepsy.

Release form

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

Acetylcholine chloride is a drug from the group of m- and n-cholinomimetics, it has a stimulating effect on m- and n-cholinergic receptors.

What is the action of acetylcholine chloride?

M-cholinomimetic action will be manifested by bradycardia, the tone will increase, as well as the contractile activity of the muscles of the bronchi, bladder, gastrointestinal tract, as well as the ciliary muscle of the eye. In addition, the secretion of the salivary, lacrimal glands, bronchi, stomach, and intestines will increase. The sphincters of the bladder and gastrointestinal tract will relax under the influence of this drug.

The N-cholinomimetic effect of the drug Acetylcholine chloride is associated with the participation of the substance acetylcholine in the transmission of nerve impulses to the postganglionic vegetative nodes and to the striated muscles. IN small doses this agent is considered a transmitter of nervous excitation, and in large cases it leads to persistent depolarization in the synapse region, which leads to blocking of the transmission of excitation.

The drug Acetylcholine chloride is directly involved in the transmission of nerve impulses in many parts of the brain, while in high concentrations it inhibits synaptic transmission, and in small concentrations it facilitates.

What are the indications for Acetylcholine Chloride?

I will list some conditions in the presence of which it is indicated to use the drug Acetylcholine chloride:

The patient has endarteritis;
With intermittent claudication, this is also used medicinal product;
Its use is also shown for trophic disorders in the stumps;
The remedy is also effective in the presence of spasms of the arteries of the retina;
It is used for intestinal atony, as well as for decreased bladder tone.

In addition, acetylcholine chloride is used to alleviate x-ray examination if there is such pathological process like achalasia of the esophagus.

What are the contraindications for the use of the drug Acetylcholine chloride?

Among the contraindications Acetylcholine chloride, instructions for use give the following conditions:

This product must not be used when bronchial asthma;
In the presence of angina, Acetylcholine chloride is also contraindicated;
Do not use it for severe atherosclerotic processes in the human body;
Do not prescribe the drug for epilepsy;
With lactation;
When bleeding from digestive tract;
With hyperkinesis;
Its use is contraindicated in all trimesters during pregnancy.

If the patient has any inflammatory processes, localized in abdominal cavity before surgical intervention, in this case Acetylcholine is also contraindicated.

What is the use and dosage of Acetylcholine Chloride?

This drug is used parenterally, namely, it is administered subcutaneously or intramuscularly, while the dosage can be 50-100 mg, the frequency of use should not exceed three times during the day. Maximum doses Acetylcholine chloride is as follows: single - 100 mg, and the daily amount is not more than 300 mg.

When used simultaneously with anticholinesterase agents, the cholinomimetic effect of Acetylcholine chloride is markedly enhanced.

At joint application m-anticholinergics, antipsychotics (clozapine, phenothiazine, chlorprothixene), as well as tricyclic antidepressants, the effect of Acetylcholine chloride decreases. It should be noted that this drug is not used during the period breastfeeding as well as during pregnancy.

What are the drugs Acetylcholine chloride side effects?

When using Acetylcholine chloride, the manifestation of side effects is not excluded, for example, from digestive system there may be nausea, vomiting, the patient will complain of pain in the abdomen, besides this joins liquid stool, there are signs of salivation.

From the side of cardio-vascular system side effects may also appear, in particular, bradycardia will appear, in addition, the patient may complain of low blood pressure.

Others may be noted side effects, they will appear increased sweating, to join rhinorrhea, bronchospasm is not excluded, in addition, a person may feel frequent urination.

From the side of the nervous system it is noted headache, in addition, accommodation is disturbed, lacrimation joins. At explicit manifestation side effects, it is recommended to consult your doctor.

special instructions

Currently, the use of Acetylcholine chloride is limited in terms of systemic use, but it is included in the composition combined drugs For local use in ophthalmic surgery, in order to create a rapid constriction of the pupil of the so-called miosis.

Preparations containing Acetylcholine chloride (analogues)

Acetylcholine chloride is contained in the drug of the same name, it is produced in dosage form, which is represented by a fine powder, it is necessary to prepare medicinal solution which is intended for intramuscular injection, as well as for subcutaneous injection. It must be used before the expiration date indicated on the package.

Often this drug is used in ophthalmology, for example, with surgical intervention on the anterior chamber of the eye, in particular, for the removal of an existing cataract, for iridectomy, as well as for keratoplasty. As a result of the use of Acetylcholine chloride, pupil constriction is provided for some time.

Conclusion

Before using the drug, you should consult with your doctor.