SYMPATHOLYTICS [lat. (systema nervorum) of sympathicum a sympathetic nervous system + the Greek lytikos clearing, weakening] — the pharmaceuticals eliminating influence of a sympathetic innervation on executive bodies as a result of selective impact on bombways of axons of postganglionic adrenergic neurons. Working presynaptically, S. pages do not interfere with influence of direct adrenomimetik (noradrenaline, etc.) and even strengthen their effect. Villages of the village consider as one of subgroups so-called. anti-adrenergic means (see).
Properties C. of page were for the first time found in a ksilokholin (TM-10) and other 2,6-xylilac ethers of sincaline.
On a chemical structure among S. the page can be allocated: connections of quarternary structure — ksilokholin, Ornidum (see); derivatives of guanidine — Octadinum (see), betanidin, guanoxan; derivatives of amidine — debrisoquine (a synonym deklinaks); alkaloids of Rauwolfia — Reserpinum (see), deserpidine, restsinnamin; alpha metilirovannye aromatic amino acids — Methyldopa (see) and alpha methyl - L - tyrosine.
In total S. the page of the specified groups suppress function of adrenergic neurons, reducing finally quantity mediator (see), released in a synaptic gap by nervous impulse. However drugs of each of these groups cause this effect in the different ways. So, S. pages of quarternary structure break permeability of presynaptic membranes for calcium ions, receipt to-rykh inside adrenergic axons at the time of their excitement is an important element of the mechanism of pulse release of a mediator. In this regard S. pages of quarternary structure interfere with the release caused by nervous impulse noradrenaline (see). In an experiment such S.' introduction by the village after an injection of radioactive noradrenaline leads to increase in contents of the last in adrenergic neurons. Along with this S. pages of quarternary structure oppress the return capture of a mediator, reducing the maintenance labilno of the connected noradrenaline. It significantly does not affect the general maintenance of the mediator accumulated generally in synoptic bubbles, but sympathomimetic effect of tyramine or ephedrine, action to-rykh is caused by release labilno of the connected mediator, is a little weakened.
Braking of pulse release of noradrenaline matters also in the mechanism of action of S. of page from group of derivatives of guanidine in this connection drugs of this group (Octadinum, etc.) break momentum transfer from sympathetic nerves earlier, than under their influence there comes a little considerable exhaustion of stocks of noradrenaline in adrenergic neurons. The most important component of the mechanism of sympatholytic action of derivatives of guanidine is the inhibition of the transport system which is carrying out the return capture (return) of the mediator released in a crack of an adrenergic synapse under the influence of nervous impulse. The transport system of a presynaptic membrane, apparently, is capable to move in an axon not only a mediator, but also S. of page from group of derivatives of guanidine. Transport of the last this system excludes a possibility of the return capture of a mediator axons. Guanidinovy S.' accumulation by the village in axons is followed by replacement of noradrenaline from vesicular and extra vesicular depots. The forced-out mediator partially collapses in an axon under the influence of MAO. A significant amount of not destroyed mediator is allocated in a synaptic gap and further in the general blood circulatory system, causing an initial sympathomimetic phase of action of derivatives of guanidine, duration the cut makes apprx. 1 — 3 hour. The page of this group leads exhaustion of stocks of noradrenaline in adrenergic neurons under the influence of S. to oppression of function of sympathetic nerves. For the same reason derivatives of guanidine eliminate effects of tyramine and ephedrine.
Reserpinum and related to it alkaloids of Rauwolfia it is irreversible block system of transport of monoamines (dopamine, noradrenaline) through a membrane of synoptic vesicles. The monoamines remaining in cytoplasm collapse under the influence of MAO almost completely in this connection the sympathomimetic phase of action at Reserpinum is expressed poorly. Disturbance of intake of dopamine in vesicles at action of Reserpinum leads to decrease in synthesis of noradrenaline. Thus, though Reserpinum does not force out noradrenaline from granules and does not influence system of the return transport of a mediator through a presynaptic membrane, it gradually devastates stocks of both vesicular, and extra vesicular noradrenaline that is followed by oppression of function of adrenergic neurons. Like derivatives of guanidine Reserpinum eliminates effects of indirect sympathomimetics (ephedrine, tyramine).
Villages of the village from number and-metilirovannykh amino acids get into adrenergic neurons and partially inhibit the DOFA-decarboxylase, breaking at the expense of it synthesis of noradrenaline. At the same time under the influence of the specified enzyme C. of page of this group turn in and - me-tilirovannye amines (and - metilnorad-renalin, metaraminol), to-rye collect in depot instead of noradrenaline and perform function of the so-called false mediators having smaller postsynaptic activity than a true mediator. At the same time false mediators (especially and - methylnoradrenaline) are powerful activators presynaptic an a2-adrenoretsepto-ditch. Affecting these adrenoceptors, false mediators break pulse release of noradrenaline from bombways of adrenergic axons. Besides, false mediators (especially metaraminol) can work as inhibitors of the return capture of noradrenaline with axons of adrenergic neurons.
Reducing sympathetic influences on heart and vessels, S. pages significantly lower the ABP (systolic and diastolic), reduce the central venous pressure and venous return of blood to heart. The hypotensive effect of Octadinum and Reserpinum is usually preceded by a phase of increase in the ABP. At introduction of Ornidum and Methyldopa the hypotensive effect reaches a maximum in 3 — 6 hours and proceeds till 6 — 12 o'clock. At oral administration of Octadinum the maximum hypotension develops in 2 — 3 days, and at use of Reserpinum — in 4 — 6 days. After their cancellation the ABP remains reduced during 2 — 4 weeks. The hypotensive effect of S. of page is originally caused by decrease in cordial emission, to-ry is normalized in process of reduction of the general peripheric resistance. At prolonged use of S. of page the hypotensive effect gradually decreases in view of a delay of ions of sodium and water in an organism and increases in mass of the circulating blood. Accustoming to Ornidum develops especially quickly.
Villages of the village of quarternary structure do not get, and derivatives of guanidine badly get through a blood-brain barrier. Reserpinum and Methyldopa easily get into a brain and moderately (Methyldopa) or considerably (Reserpinum) reduce contents in c. N of page of noradrenaline, dopamine and serotonin. Connect sedative action of Methyldopa, and also sedative and antipsychotic effects of Reserpinum with it. Kloni-dinopodobnoye presynaptic action and - the methyl-hole of the drenalin which is formed of Methyldopa in adrenergic synapses of a myelencephalon is the cornerstone of the oppressing effect of this drug on the centers of vasculomotor regulation.
Apply S. of page of hl. obr. as antihypertensives (see) for treatment of an idiopathic hypertensia of the II—III stage. Ornidum and Reserpinum use also at nek-ry types of cardiac arrhythmias, especially at takhisistolichesky. Villages of the village are contraindicated at crushing organic lesions of heart, acute disorders of cerebral and coronary circulation, insufficiency of secretory function of kidneys, a peptic ulcer of a stomach and a duodenum. It is not necessary to appoint Reserpinum and Methyldopa in cases when in the anamnesis there are instructions on episodes of a depression.
Side effect at treatment by Ornidum is observed rather seldom. Other S. pages cause the side effects connected with dominance of a tone of a parasympathetic innervation (strengthening of motor and secretory functions of a stomach and intestines). Under the influence of S. of page many patients have a difficulty of breath through a nose owing to swelling of mucous membranes of a nose. At purpose of Methyldopa and Reserpinum weakness, drowsiness, a depression can be noted. Villages of the village promote a delay of sodium and water in an organism. Orthostatic collapse (see) more often develops at use of Octadinum and occasionally — Methyldopas. Pages of this side effect practically do not cause other S. In addition to the listed above side effects, allergic reactions are possible (see. Allergy ), to-rye a thicket are noted under the influence of a medshdofa. There are messages that sometimes at reception of Methyldopa autoimmune develops hemolitic anemia (see).
For stopping of the orthostatic collapse caused by S. page use angiotonic means (noradrenaline, a phenylephine hydrochloride). At the side effects connected with dominance of a tone of a parasympathetic nervous system apply holinoblokiruyushchy means (e.g., Methacinum, etc.). For correction of a hypervolemia along with S. pages appoint diuretics (a dichlothiazide, Spironolactonum, etc.).
Bibliography: Avakyan O. M. Pharmacological regulation of release and capture of noradrenaline, Yerevan, 1973, bibliogr.; Clinical pharmacology, under the editorship of V. V. Zakusov, M., 1978; To ohm and with with and r about in I. V. Medicinal regulation of adrenergic processes, Kiev, 1976; Pharmacology of monoaminergichesky processes, under the editorship of V. V. Zakusov and N. V. Kaverina, M., 1971; Bou of hectare A. L. a. Green A. F. Adrenergic neurone blocking agents, Ann. Rev. Pharmacol., v. 5, p. 183, 1965, bibliogr.; To op in I. J. False adrenergic transmitters, ibid., v. 8, p. 377, 1968, bibliogr.; The pharmacological basis of therapeutics, ed. by A. G. Gilman and. lake, N. Y., 1980.
I. V. Komissarov.