Adrenaline and Adrenomimeticalkie substance
Epinephrine was first detected in extracts of the adrenal glands in 1895. In 1901, was the synthesis of crystalline adrenaline. Soon adrenaline has found application in medicine for high blood pressure in the collapse, to narrow the blood vessels under local anesthesia, and then for the relief of asthma attacks.
In 1905 it was found important physiological significance of adrenaline. Based on the similarities with the effects of adrenaline effect observed during stimulation of sympathetic nerve fibers, it has been suggested that the transmission of nerve excitation of sympathetic nerve endings on the effector cells is carried out with the assistance of a chemical transmitter (mediator), which is adrenaline or adrenolinopodobnye substance. This was the beginning of the teaching of chemical transmission of nerve excitation.
In the future, the process of biosynthesis of adrenaline was discovered, starting from the amino acid tyrosine, through dihydroxyphenylalanine (L-DOPA), dopamine, norepinephrine to epinephrine.
In 1946, it was establishing that major mediator adrenergic (sympathetic) transfer is not the adrenaline and noradrenaline. Resulting in the body endogenous adrenaline partially involved in the processes of the nervous excitement, but mainly plays the role of hormonal substances, affecting the metabolic processes.
Norepinephrine performs mediator function in peripheral nerve endings and synapses in the central nervous system. Biochemical system tissues that interact with norepinephrine, called adrenergic (adrenergic) systems, or adrenergic receptors ( "adrenoceptor".). According to modern concepts, norepinephrine, stands out in the course of the nerve impulse from the presynaptic nerve terminals affects the cell membrane adenylate cyclase noradrenalinochuvstvitelnuyu adrenoceptor system, which leads to increased intracellular formation of 3'-5'-cyclic adenosine monophosphate (cAMP), which plays the role of "secondary" transmitter ( a mediator), the activation energy compounds biosynthesis and further to implement adrenergic physiological effects.
An important role in the transmission of impulses in the central nervous system also plays a dopamine is a chemical precursor of norepinephrine, but performs independent neurotransmitter role (see. Dopamine, Neuroleptics, Means for treatment of Parkinson's disease).
Following the discovery of adrenalin activities, work began on the production of adrenalin substance synthetically. As a result, a large number of drugs as adrenopozitivnyh, ie stimulating adrenergic processes, and adrenonegativnyh -.. Antiadrenergic substances.
Modern medicine has a significant amount of these funds, including adrenaline and noradrenaline (currently receiving synthetically) and a number of "exogenous" synthetic adrenopozitivnyh drugs (phenylephrine, Phethanolum, izadrin, salbutamol, ortsiprenalin, fenoterol, dobutamine, etc..), Blockers (phentolamine, tropafen, prazosin, propranolol, or propranolol, atenolol, pindolol, etc..) and other substances, the effect of which is associated with the effect on the adrenergic processes. According to the chemical structure of these agents in varying degrees, noradrenaline and adrenaline are related, and their main pharmacological properties relate primarily to the interaction with specific adrenergic receptors of effector cells.
Adrenergic receptors, for which nature, ie. E. Endogenous ligands are norepinephrine and epinephrine, originally designated in general terms as the adrenergic receptors. However, the study of action of these features endogenous compounds and their synthetic analogs and derivatives led to the conclusion that heterogeneity adrenoceptor presence of subgroups of different localization and functional significance. First, they were divided into - and ~ -adrenoceptors and then ~ - and - ~ - and -adrenoceptors. The identification of these subgroups is important pharmacological and clinical significance. Effect on different adrenergic receptors defines not only the features of the pharmacological actions of various adrenergic and antiadrenergic substances, but also the indications and contraindications for their practical use. So, inotropic cardiotonic action of adrenaline, noradrenaline, izadrina determined by their influence on ~~ adrenergic receptors localized in the myocardium; peripheral vasoconstrictor action of adrenaline, noradrenaline, mezatona - adrenoceptor stimulation; bronchodilator action of adrenaline and izadrina - adrenoceptor stimulation ~ bronchi. Strong action on the adrenergic receptors of the bronchi having salbutamol ortsiprenalin (alupent, astmopent), fenoterol (berotek) and other modern adrenomi meticheskie bronchodilators. In effect on ~ -adrenoceptors is associated gastric relaxation induced by adrenaline muscle, intestine, and uterus. Recently, as a means of relaxing the muscles of the uterus (tocolytic agents) are widely used fenoterol (partusisten), terbutaline, salbutamol (salbupart) and other selective adrenoceptor stimulants ~~. Of ~ blockers Inderal (propranolol) simultaneously acts on ~~ - and -adrenoceptors and its antiischemic, antiarrhythmic and antihypertensive action may be accompanied by side effects (bronchoconstrictor; increased peripheral vascular resistance), while the other selective atenolol adrenoblokatory acting by ~, myocardial adrenergic receptors, such side effects do not cause. Created agents that combine the blocking effect on the ~ - and adrenergic receptors (labetalol, etc.). Selective blocker of postsynaptic ~ adrenoceptor is prazosin and clonidine, guanfacine, -metildofa (dopegit) ~ stimulate the central adrenergic receptors.
Drugs that affect the function of various adrenergic receptors, are currently widely used in various fields of medicine.
Subgroup Means acting on peripheral adrenergic processes include medications:
- Adrenaline (Adrenalinum)
- Flomax (Berodual)
- Galazolin (Halazolinum)
- Hexoprenaline (Hexoprenaline)
- Dobutamine (Dobutaminum)
- Defedrin (Dephedrinum)
- Izadrin (Isadrinum)
- Indanazolin (Indanazoline)
- Clenbuterol (Clenbuterol)
- Mezaton (Mesatonum)
- Naphthyzinum (Naphthyzinum)
- Noradrenaline tartrate (Noradrenalini hydrotartras)
- Oxymetazoline (Oxymetazoline)
- Ortsiprenalina sulfate (Orciprenalini sulfas)
- Salmeterol (Salmeterol)
- Salbutamol (Salbutamolum)
- Tetryzoline (Tetryzolin)
- Fenoterol (Fenoterolum)
- Fetanola (Phethanolum)
- Formoterol (Formoterol)
- Ephedrine (Ephedrinum)