Nentski was opened Histamine in 1876. It is a biogenic compound produced in the body in the decarboxylation of amino acid histidine. Histamine can also be produced by microorganisms present in the respiratory tract (Branchamella catarhalis, Haemophilus parainfluenzae, Pseudomonas aeruginosa). It is a component of certain poisons and secrets, irritating.
Under normal conditions, histamine is stored in granules of mast cells and basophils bound, inactive state. Various pathological States (anaphylactic shock, burns, frostbite, hay fever, hives and other allergic diseases), as well as intake of some chemical substances liberator accompanied by the release of histamine from the depot. Liberatore histamine are, in particular, d-tubokurarin, morphine, Radiocontrast iodine-containing drugs, poliglyukin and other high-molecular compounds. When allergic reactions of pre-sensitized mast cells histamine is released together with generated mediators (leukotrienes and prostaglandins). Secretion of histamine is a consequence of the interaction of s3a and s5a component of complement with specific membrane receptors, or the result of binding to the antigen in fixed cells, IgE. The maximum concentration of histamine in the blood is recorded in 5 min after its release in reactions of immediate hypersensitivity, and then it rapidly diffuses into the surrounding tissue. Free histamine causes spasm of smooth muscles (including muscles of the bronchi), the expansion of capillaries, and hypotension. Due to the action of histamine stasis of blood in the capillaries and increased permeability of their walls is accompanied by swelling of the surrounding tissues. In connection with the reflex excitation of the adrenal medulla secretes epinephrine (narrowing of arterioles and tachycardia). Histamine stimulates the secretion of gastric juice.
Only 2-3% of histamine is excreted unchanged, the remaining part is metabolized with the participation of diaminoksidazy to imidazoluksusnoy acid.
In 1950-55. Ash and Schild hypothesized that the effect of histamine is mediated through at least two subtypes of receptors: H1 and H2. In recent years it has become apparent that histamine is not only a mediator of some pathophysiological States, but also functions as a neurotransmitter. In 1983, J.-M. Arrang et al. identified in the CNS of a new subtype histaminergic receptor — H3.
H1-, H2-, H3-receptor conformation and different tissue localization. Stimulation of histamine H1-receptors causes vasodilation, increased vascular permeability, bronchial smooth muscle spasm and bowel. The most characteristic for the excitation of H2 receptor is increasing the secretion of the gastric glands. H2-receptors are involved in the regulation of the functions of the heart, the smooth muscle tone of the uterus, intestines, blood vessels. Together with H1 - receptors are involved in allergic and immune responses. In the CNS presents all three types of histamine receptors: H1 - and H2-receptors are located on postsynaptic membranes, N3 - localized mainly presynaptic. The stimulation of H3 receptors inhibited the release of the nerve endings of a number of mediators, including histamine, inhibited the transfer of excitation in the sympathetic nervous system. Through them mediated by such functions as sleep/wakefulness, hormonal secretion, cardiovascular control, etc. Studies conducted in recent years give grounds to count on the possibility of establishing special funds, acting on H3-receptors, for the treatment of diseases of the Central nervous system, including stimulants of cognitive functions for the treatment of Alzheimer's disease and other senile dementias, psychoses, and epilepsy.
There are two groups of drugs affecting histaminergic transmission: gistaminolitiki (directly stimulate receptors or increase the content of free endogenous histamine) and gistaminolitiki. Last, interacting with the receptor, prevent the binding of histamine with them, or lower the level of free histamine in the body.