Histamine

HISTAMINE, Histamin s. Ergamin, chemically represents /S-imidazolyl-aethyl-amin, being an amine derived from the amino acid histidine; structural formula: ,nh-сн не/ |: ^N-----C-CH₂-CH,-РГН,. H. is a colorless crystalline substance; melting point 83-84°; boiling point 209-210°; easily soluble in water and alcohol, insoluble in ether. The hydrochloride salt of H. (Histaminum dichlorhydratum- C₆H_ftN₃. 2HC1) is easily soluble in water and ethyl alcohol; melting point 240°.-H. may appear as a result of protein decomposition during putrefaction. Among other things, it was extracted from intestinal contents. Some of it, along with other proteinogenic amines, is found in preparations of ergot. H. or amines similar to it may be present in extracts of the mucous membranes of the digestive tract, as well as in extracts of other organs, and in its formation under these conditions, the role of bacteria cannot be excluded.-H. has an exciting effect on smooth muscles, especially on the uterus, for which reason attempts were made to use it as a uterine agent.-Preparations: Imido-Roche = sol. /Mmidazolyl-aetriylamin chlorhydr. 1:1.000; Tenosin (Bayer) 1 cubic cm = Histamine 0.125 mg + Tyramine 6.25 mg. However, due to its general toxicity, this substance has not found acceptance as a therapeutic agent and has only toxicological interest, especially in view of the possibility of its presence in organ preparations. - Symptoms of H. poisoning vary in different animals. In carnivores (cats, dogs), upon injection of H., a fall in blood pressure is observed, which is explained by paralysis of the capillaries of the systemic circulation. The animal dies as if from blood loss, which fills the dilated capillary network. At the same time, transudation of liquid parts of the blood into tissues increases, causing its thickening (relative increase in formed elements). Some authors consider the spasm of hepatic veins occurring under the influence of H. and the resulting decrease in blood flow to the heart as the main cause of the fall in blood pressure, which is especially manifested in dogs. The described fall in blood pressure is absent in herbivores, particularly in rabbits. In the latter, intravenous administration of H. increases blood pressure due to its constricting effect on arterioles. On isolated organs nourished by Ringer-Locke solution, H. has a vasoconstrictive effect. On the heart, it acts as a stimulant, but with large doses in experiments on the whole animal (carnivore), heart activity decreases, probably due to impaired nutrition as a result of a sharp decrease in blood pressure. Smooth muscles under the influence of H. go into a state of spasm. The musculature of the uterus is especially sensitive to H.; the intestine, stomach, and bronchial muscles also go into a state of spastic contraction. The latter symptom is especially pronounced in rodents,-guinea pigs die from H. with symptoms of suffocation from bronchial spasm. The secretion of glands (salivary, gastric, pancreatic, lacrimal) is stimulated under the influence of histamine. H. is relatively quickly neutralized in the body and therefore with slow methods of administration (especially per os) it is little active. With careless use of H. in humans, the following toxic phenomena have been described: redness of the face and conjunctiva, fall in blood pressure, rapid pulse, dizziness, nausea, general weakness. In severe cases-the picture of collapse. At the site of H. injection, redness and infiltrate are observed, which is explained by the local action of the poison on capillaries. The similarity of H. poisoning symptoms with the symptoms of traumatic shock gave rise to the hypothesis that in the latter, H. or histamine-like substances formed in damaged tissues are to blame (Dale). It is also interesting the similarity that the symptoms of H. poisoning in different animals present with the main symptoms of anaphylactic shock in the same species. However, it is hardly this similarity can be sufficient reason to attribute to H. any role in the mechanism of anaphylaxis.-Histamine was adopted by Ph VII as a standard in the standardization of uterine agents - ergot preparations and pituitrin. Its use for this purpose, especially in relation to pituitrin, meets great objections mainly because the sensitivity of the uterus to pituitrin and to the pharmacologically non-identical H., depending on various conditions and on the individuality of the organ, varies differently. Recently, H. has been used in the clinic to stimulate gastric secretion: the histamine test serves for the differential diagnosis of complete and transient achylias.