NORADRENALINE (synonym Norepinephrinum) — physiologically active agent, biogenic amine, mediator and hormone sympathoadrenal, or adrenergic, systems. The N is developed in marrow of adrenal glands, and also in accumulations of extraadrenal chromaffin fabric, in a brain and in sympathetic nerve terminations. The N is a mediator of postganglionic sympathetic nervous impulses and adrenergic processes in c. N of page (see. Mediators ); in medicine it is used as medicine, treats group adrenomimetichesky means (see). N.'s maintenance in daily amount of urine is additional diagnostic test at nek-ry diseases, napr, at a pheochromocytoma.
From adrenaline (see) on a chemical structure of N. differs in absence of methyl group at a nitrogen atom.
N, as well as others catecholamines (see), it is synthesized in an organism from amino acids tyrosine (see) and phenylalanine (see). In N.'s biosynthesis active part is taken by a tyrosine-3-hydroxylase (KF 18.104.22.168), edges are limited by the speed of synthesis of N. since catalyzes the main reaction of process — a hydroxylation of tyrosine to DOFA. Direct education of N. from dopamine catalyzes dopamine — a beta hydroxylase (KF 22.214.171.124). Laevoisomer H. many times over surpasses D-noradrenaline in pharmakodi-namichesky activity. N. formed in sympathetic neurons is localized in special granules (vesicles), accumulating in nerve terminations. Usually N. contains in them in the form of a complex with ATP and specific protein — dromograniny. Under the influence of nervous impulse, and also at action of a number of chemical factors contents of granules are allocated in a synaptic gap (the most probable mechanism of emptying of granules the exocytosis is) and specifically affect adrenoreaktivny system. Considerable part H., allocated at nervous impulse, is taken in adrenergic neuron (so-called neyronalny capture or capture-1) again, and a nek-swarm N.'s number diffuses in the general blood stream, at the same time a part of the released N. is absorbed by body tissues (so-called ekst-raneyronalny capture or capture-2). N.'s elimination from a synaptic gap provides the bystry termination of its action on adrenoceptors. The special form of capture of N. is its transition from cytoplasm of neuron to vesicles (so-called vesicular capture); at disturbance of this process of N. quickly is oxidized in cytoplasm of neuron monoamine oxidase (see). Reserpinum and its derivatives block this form of capture, causing reduction of stocks of N. in nerve terminations.
N.'s transformation is carried out generally by its consecutive O-methylation and oxidizing deamination to Z-metoksi-4-oksimindalnoy to - you, and also quinoid oxidation, conjugation etc.; take part in N.'s catabolism noradrenaline — N-metiltransferaza (KF 126.96.36.199) and monoamine oxidase. A metabolite of noradrenaline — 3-metoksi-4-hydroxy-mandelic to - that and its derivative — Z-metoksi-4-oksi-fenilglikol have no properties of hormone, but there are data that they participate in regulation of exchange of glucose in muscles, and also in heart, a brain, a liver and other bodies. Normetanefrin (product of O-methylation of N.) — the weak sympathomimetic, but active inhibitor of ekstraneyronalny taking
of N. Fiziologicheski N.'s action very much reminds effect of stimulation of adrenergic nerves. However N.'s action in many respects differs from effect of adrenaline (see the table). Believe that these hormones not only are produced by different cells, but also cosecrete separately, depending on requirements of an organism. Aggressive, active emotions, crossclamping of carotid arteries are caused preferential by N.'s release, and a hypoglycemia, irritation of a sciatic nerve and painful incentives — release of adrenaline. The N first of all influences cardiovascular system: it is released in response to change of a pose, physical. work, bleeding, i.e. in response to such incentives, to-rye are demanded by reorganizations of a hemodynamics. The N is a strong vasoconstrictor. It causes increase in both the systolic, and diastolic ABP (see. Blood pressure ), what reflex can lead to the expressed bradycardia. In turn adrenaline is released in response to pain, an injury and other incentives, to-rye cause reaction from a metabolism.
Adrenaline is more powerful inhibitor of smooth muscles, than H.
However, as well as adrenaline, N. is membranotropny substance, its interaction with the receptors which are built in a membrane is followed by activation of cyclases - ache systems, change of contents in an effector cell of cyclic nucleotides — cyclic 3', 5' - AMF or 3', the 5th '-guanozinmono-phosphate, activation of protein kinases (KF 188.8.131.52). Lack of stage of latency and proportionality of intensity of reaction to amount of the emitted or entered substance is characteristic of N.'s action and adrenaline. As well as adrenaline, N. is emitted at allergic reactions of immediate type in the quantities exceeding normal amounts (see. Allergy ).
The number of N. coming to a blood stream in fiziol conditions, makes apprx. 0,5 — 1 mkg a minute and 0,7 — 1,4 mg a day. Normal blood contains 0,4 mkg of N. in 1 l, in daily amount of urine — 6 — 40 mkg of N.
Increase in concentration of N. in urine is noted at to a pheochromocytoma (see), in a maniacal phase maniac-depressive psychosis (see), at myocardial infarction (see) and other diseases. Determination of content of N. in blood and urine is carried out by colorimetric, flyuorimetrichesky, hromatografichesky and other methods (see. Catecholamines, methods of definition ).
Noradrenaline as drug
Noradrenaline hydrotartrate (Noradrenalini hydrotartras; synonym: Norepinephrine, Levarterenoli bitartras, Arterenol etc.; GFH, joint venture. B) — the white crystal powder which is growing brown under the influence of light and oxygen of air. Let's easily dissolve in water, it is bad — in alcohol. Water solutions (pH 3,0 — 4,5) will sterilize at 100 ° within 15 min.
N. apply to increase in the ABP, at a collapse and shock of various origin.
Enter N. intravenously kapelno at the rate of 4 — 8 mg (2 — 4 ml of 0,2% of solution) for 1 l of 5% of solution of glucose. Speed of injection usually makes 20 — 60 drops in 1 min. and is regulated on change of the systolic ABP, a cut it is recommended to support at the level of 100 mm of mercury. Therapeutic doses for the adult make 3 — 12 mkg of N. in 1 min. Subcutaneously it is impossible to enter N. because of probability of formation of necroses.
Side effects note seldom. Sometimes there are a headache, heartbeat, difficulty of breath, feeling of alarm. At overdose there is a krizopodobny build-up of pressure with severe head and retrosternal pains, a photophobia, pallor, perspiration.
Use of N. contraindicated in cases, when pe to a condition of the patient dangerously essential increase in the ABP (the expressed atherosclerosis of vessels of a brain, a left ventricular failure, coronary insufficiency of the III degree, etc.). N.'s introduction is contraindicated at a ftorotanovy, cyclopropane and chloroformic anesthesia.
Form of release: ampoules on 1 ml of 0,2% of solution to store in the place protected from light.
Table. The comparative characteristic of effect of adrenaline and noradrenaline on a homeostasis [across Grollmen (A. Grollman, 1964)]
Bibliography: Biochemistry of hormones and hormonal regulation, under the editorship of N. A. Yudayev, M., 1976; Komissarov I. V. Medicinal regulation of adrenergic processes, Kiev, 1976; M and t of l and - N and E. Sh. and Menshikov V. V. Clinical biochemistry of catecholamines, page 7, etc., M., 1967; Menshikov V. V. Methods of clinical biochemistry of hormones and mediators, p. 2, page 24, etc., M., 1974; At A. M tevskiya. Catecholamines as regulatory and bio-catalytic factors in the general system of biogenic amines, in book: Fiziol, and biochemical, biogenic amines, under the editorship of V. V. Menshikov, etc., page 5, M., 1969; Physiology of endocrine system, under the editorship of V. G. Baranov, page 326, etc., Minsk, 1979; Euler U. S. Noradrenaline, Springfield, 1956; Hormones in blood, ed by of Page H. Gray a. V. H. T. James, v. 2, p. 143, L. a. o., 1979; Monoamine oxidases, new vistas, ed. by E. Costa a. M. Sandler, N. Y., 1972; The pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Gilman, p. 422, N. Y. a. o., 1975.
A. M. Utevsky; I. V. Komissarov (pharm.).