HOLINOLITYCHESKY SUBSTANCES (sincaline + Greek lysis release, disposal; synonym: the well-cared
blocking substances, holinonega-tivny substances) — and central care-noretseptory for the natural and synthetic compounds having ability to block peripheral. X. reduce sensitivity of these receptors to action of acetylcholine and other cholinomimetics century.
Classification of X. it is based on idea of existence of two types of holinoretseptor century: the m-holino-receptors sensitive to muscarine, and the N-holinoretseptorov sensitive to nicotine (see the Autonomic nervous system, physiology). According to it distinguish m - cholinolytic (m-care-noblokatory) also for N - cholinolytic means (N-holinoblokatory). On the main orientation of action on peripheral and central holinoretseptor among X. distinguish drugs preferential peripheral century (peripheral cholinolytics) and the central action (the central cholinolytics). To peripheral X. century, as a rule, connections, e.g. Methacinum belong (see), at a molecule to-rykh there are one or two onium quarternary groups interfering penetration of substances through a blood-brain barrier (see). Tertiary connections along with peripheral have the expressed central cholinolytic effect, and at one drugs, napr, at amizyl (see), the central action, and at others, napr, at atropine (see) — peripheral can prevail.
Selectivity of action of X. century on m - and the N-holinoretseptory varies over a wide range: along with drugs of strictly selective effect on separate types care-noretseptorov among X. there are connections century, at to-rykh m - and by N - cholinolytic effects are combined. Such drugs carry to m - and N-holino to litika (m - and N-holinoblokatoram), or X. century of the mixed action. In each of the groups X stated above. century the drugs entering them classify by a chemical structure.
Action of X. it is caused century by their ability to suppress fiziol. effects of acetylcholine (see) and cholinomimetic substances (see) in all bodies having a vegetative innervation and also in c. N of page. In this regard X. have therapeutic effect at patol century. the states which are followed by the expressed hyperfunction of cholinergic systems.
In spite of the fact that X. belong to various classes of chemical connections century, they keep lines of looking alike acetylcholine. Difference of X. century on a structure from acetylcholine comes down to the fact that in a molecule X. there are «enlarged» hydrophobic radicals century. Possessing more complex chemical structure, than acetylcholine, X. interact with holinoretseptor in bigger number of points century that defines their higher stereospecificity in comparison with acetylcholine. So, according to S. V. Anichkov, molecules of m cholinolytics react with care-noretseptorom in three of its points: the anion center of a receptor interacts with cationic group of a molecule X. century; other point a holinoretsep-Torah reacts with oxygen atom in radio group of a molecule of m cholinolytics; the third point the holinoretsep-Torah reacting with oxygen of carbonyl group of acetylcholine interacts with the active group of a molecule corresponding to this oxygen atom hm-holino-litikov.
At interaction of acetylcholine and other cholinomimetics to active centers of m-holinore-tseptora there is a deformation of the last owing to what permeability of a postsynaptic membrane for cations increases. Unlike cholinomimetics of X. do not deform century, and only connect («occupy») a holinoretseptor thanks to existence in it around functional groups of the respective fields capable to enter in connection with hydrophobic radicals of molecules X. century. Emergence of such bonds interferes with deformation of a holinore-tseptor. Explain these antagonism between m cholinolytics and acetylcholine concerning sincaline of receptors. According to S. G. Kuznetsov and S. N. Golikov (1962) assumption the active center of m-holinoretseptora is located on two neighboring sites of the proteinaceous chains connected among themselves by ionic, hydrogen and other rather fragile strengths. Molecules X. terminate these communications century, forming from sincaline a receptor stronger connection, than with acetylcholine is considerable.
Cholinolytic substances of preferential peripheral action divide into m-holino of a liti-ka, N cholinolytics, m - and N-holino-litiki. Refer two groups of connections to m cholinolytics. Atropine (see) and other alkaloids — Scopolaminum (see), Platyphyllinum belongs to the first of them (see), the second group quaternary ammonium salts — derivatives of atropine (methylnitrate of atropine) and Scopolaminum (methobromide of Scopolaminum), and also close to them on a structure make numerous synthetic substances of various classes (aminoethers, amino alcohols, aminoamides, etc.) in the form of quaternary salts. The action which is the most expressed to selective m-holinolitp-cheskim quaternary salts of aminoalkilovy ethers two-replaced glycolic to - t possess, to the Crimea Methacinum (see), oksifenoniya, bantin, probanthene of N other belongs. The bantin and probanthene in addition to m - cholinolytic properties have a moderate ganglio-blocking action.
X. century, the possessing N-holinoli-ticheskoy activity, divide into two groups: selectively I affect
shchy N-holinoretseptory vegetative gangliyev — gaigliob the varnishing means (see), and the substances which are selectively operating on N-holinoretseptory in the terminations of motor nerves — kurarepodob-ny substances (see).
The simplest on a structure ganglioblokiruyushchy drug: tetraethylammonium is. During the replacement in its molecule of one of radicals at nitrogen on more difficult, than ethyl, ganglioblokiruyushchy activity increases.
Some other way increases in activity accession to a molecule of additional ammonium group, i.e. creation of bis quaternary salt is. Such salts form stronger bonds with a receptor. By this way many effective ganglioblokator applied in modern medical practice, napr, Pentaminum (see), kamfoniya (see), Dimecolinum (see) of gigroniya are received (see), etc. Ganglioblokiruyushchy activity also nek-ry secondary and basic nitriles, e.g. Nanophynum (see), Pyrilenum (see), and also alkaloid Pachycarpinum have (see).
On the mechanism of action on N-holinoretseptory of skeletal muscles a chicken of a repo dobny substances divide into depolarizing and I do not depolarize - shchiye anti-depolarizing). From the drugs used in the USSR treats depolarizing ditilik (see), not depolarizing — Diplacinum (see), qualidil (see), anatruk-soniya (see), etc. Existence of two onium groups at a certain distance is characteristic of a chemical structure of kurarepodobny substances. An exception nek-ry alkaloids, napr make, Condelphinum and Mellictinum (see) which are tertiary bases. On the mechanism of action they treat the anti-depolarizing ku-rarepodobny substances.
- and N-holino to litika treat basic nitriles from among ethers m carboxylic to - t. The combination of peripheral and central m - and N-ho-linoliticheskikh of properties is characteristic of these drugs. From a large number of connections of this kind practical application found Spasmolytinum (see), aprophene (see) and thioanalogues of Spasmolytinum — Tifenum (see) and Diprophenum (see). At these drugs of m - and N - cholinolytic properties are supplemented with direct myotropic spasmolytic action (papaverinopodobny action). Drugs of this group found broad application as antispasmodics (see).
- and N cholinolytics from among quarternary amines treat m glycopyrrolate, benzpirrony bromide, tsiklopirrony bromide, etc. They are ethers disubstituted glycolic to - t, at to-rykh a quarternary nitrogen atom is in tsikli-ches which to structure (Pip Ridinovoy,
iirrolidinovy or a piper zino-howl). G1o to comparison with Spasmolytinum and other m - and N-cholinolytic-mi from among basic nitriles these drugs would possess more vyra-zhenn ymiy gan of l io in l about to and r at yushchy and
properties. In this regard they surpass basic nitriles in an anti-sekreto of rny and spasmolytic activity that favorably affects their efficiency at a peptic ulcer of a stomach and duodenum.
Cholinolytic substances of preferential central action have ability already in the minimum doses to block holino-receptors of c. N of page. Carry amizyl to the central m cholinolytics (see), mints ZIL (see), and methine, etc. They weaken convulsive and toxic effect of anti-cholinesterases-nykh and m - cholinomimetic substances, cause sedation, strengthen action of barbiturates and other hypnagogues, and also analgetics and local anesthetics. The majority of the central m cholinolytics in the doses rendering clear central effect block also peripheral m-holinoretseptory that is shown by oppression of secretion of excretory glands, the mydriasis and other effects inherent to peripheral operating m cholinolytics. However as peripheral cholinolytics it is inexpedient to apply the central m cholinolytics in connection with a possibility of development of side effects from c. N of page.
The drugs having ability to warn or suppress the spasms caused in an experiment by nicotine concern to the central N cholinolytics. Usually this action is combined with the activity which is more or less expressed ganglioblokiruyu-Russian cabbage soup. From drugs of this group in medical practice only the are a case is used so far (see), to-ry apply as cure to decrease in a muscle tone for spastic paresis of various origin.
- and N cholinolytics treat the central m Cyclodolum (see), Tropacinum (see) and Norakinum. They are used by hl. obr. as protivo-parkinsonichesky means (see).
Presence of X. century with different degree of manifestation of the blocking action concerning peripheral and central m - and the N-holinoretseptorov gives the chance to weaken by means of these substances excess cholinergic influences on internals at various levels of nervous control (central, ganglionic and postsynaptic) that allowed to develop indications to the differentiated
use of m cholinolytics, gan-glioblokator, kurarepodobny
substances and central cholinolytics. So, peripheral m cholinolytics, and also m - and N-holino - litik are applied generally as antispasmodics, ganglioblokator — as antihypertensives (see), a chicken-renodobnye of substance — as muscle relaxants (see). Atropine and other m cholinolytics, and in nek-ry cases of m - and N cholinolytics are applied also as antidotes (see) at poisonings anti-holinesteraznymi and cholinomimetic substances.
Observed at use of X. century by-effects (a mydriasis, disturbances of accommodation, tachycardia, an atony of intestines and bladder) after cancellation of drugs usually pass. The main contraindications to use of X. century glaucoma, an atony of intestines and bladder are.
Bibliography: And N and h to about in S. V. Selective effect of mediator means, L., 1974; About l and to about in S. N, and Fishzon-R y with about Yu. I. Holinoliticheskiye and adrenceptor blocking agents in clinic of internal diseases, M., 1978; Denisenko P. P. Central cholinolytics, L., 1965; Clinical pharmacology, under the editorship of V. V. Zakusov, M., 1978; The Smith about in S. G. and about l and to about in S. N. Synthetic atropinopodobny substances, L., 1962; M and sh to about in with to and y M. D. Pharmaceuticals, p.1, page 232, M., 1984; Harkevichd. And. Pharmacology, M., 1980; The pharmacological basis of therapeutics, ed. by A. G. Gilman a. o., N.Y.,
1980. C.H. Golikov.