Sympathol

SYMPATHOL, the hydrochloride salt of para-oxyphenyl-methylaminoethanol C₆H₄(OH)-CH₂CH(OH)CH₂NHCH₃, differs from adrenaline by the absence of one hydroxyl group. It was synthesized in 1926 by Legerlotz. The racemic form is commercially available. Separation into right- and left-rotating components showed greater pharmacological activity of the latter. The American firm Steams released the same substance under the name "synefrin." The melting point of the base is 184-185°C, and of the hydrochloride salt is 152-154°C. S. is a white, easily soluble crystalline powder, characterized by significantly greater stability compared to adrenaline: it is not destroyed by sterilization by boiling, is not oxidized by atmospheric oxygen, and therefore its solutions are stable during storage. Pharmacologically, like adrenaline, S. belongs to sympathomimetic substances, however it is inferior to adrenaline in the strength of its action and differs in certain features. On the isolated heart of warm-blooded animals, S. in dilutions of 1:1,000,000 and 1:100,000 exerts a marked positive ino- and chronotropic action, very similar to the adrenergic effect and only slightly inferior in strength. Experiments on the heart-lung preparation show that sympathol increases the work capacity of the insufficient heart, increasing the minute volume and eliminating venous congestion. However, as with the action of adrenaline, when the work capacity of the heart increases, oxygen consumption is disproportionately high. On blood vessels, S. has a constricting effect, but significantly inferior in strength to adrenaline; to obtain the same degree of constriction, a concentration of S. 100-200 times greater than that of adrenaline is required. On the vessels of the isolated ear, noticeable constriction is obtained from a concentration of S. 1:250,000 and stronger; concentrations of 1:25,000 usually give complete spasm. S. has the same constricting effect on the vessels of isolated human fingers (unpublished experiments of Anichkov's laboratory). With intravenous administration of S., an increase in blood pressure is observed, which, as with adrenaline, is accompanied by a slowing of the pulse due to excitation of the vagus center, but to obtain the same pressor effect, a dose of S. 100 times greater than adrenaline is required. At the same time, according to Trendelenburg's experiments, there is a significant difference in the action of S. and adrenaline: while adrenaline, even after turning off the vagus with atropine, causes an increase in blood pressure in both the left and right atria, S. does not cause such congestion in the right heart and sometimes even leads to a decrease in pressure in the right atrium. This indicates that with adrenaline, due to its relatively greater effect on blood vessels, the heart is unable to pump all the blood flowing to it into the arterial bed, whereas with S., which has a more pronounced cardiac than vascular action, such "insufficiency" of the heart is not observed. Furthermore, according to Trendelenburg's report, S. very rarely causes those disturbances of cardiac conduction and rhythm that adrenaline often causes. Administration of S. in fewer cases than adrenaline leads to ventricular fibrillation in chloroformed animals (A. Kuznetsov). This follows that S., although not entirely free from the unfavorable action on the heart characteristic of adrenaline, possesses it to a lesser degree. Unlike adrenaline, S., like ephedrine, exerts its action and increases blood pressure not only with parenteral administration but also when given orally, for which, of course, higher doses are required. The vascular action of S. under the influence of ergotoxin changes not to such a strong degree as this occurs with respect to the adrenergic effect. In this respect, S. is closer to ephedrine than to adrenaline. According to experiments on the dog's heart-lung preparation, S. dilates the coronary vessels. Subcutaneous administration of 50-100 mg of S. to healthy subjects gives a more prolonged increase in blood pressure than 1 mg of adrenaline, causing approximately the same effect in height, while oxygen consumption increases and the minute volume of blood increases by 10% to 30%. With repeated administration of S., it, like adrenaline and in contrast to ephedrine, gives approximately the same effect in strength. On smooth muscle organs, according to most authors, S. has a sympathicotonic effect and in particular relaxes the intestine and bronchial musculature. Blood sugar with subcutaneous administration of S. is slightly increased, however some authors deny both the dilating action of S. on the bronchi and the increase in blood sugar. The toxicity of S. is relatively small, and the minimum lethal dose with subcutaneous administration, according to various authors, for different animals is from 0.4 to 1.6 g per 1 kg of animal weight. Based on the pharmacology of S., it was proposed as a cardiovascular agent in vascular collapse, as well as in acute heart failure. The local action of S. can be used when added to local anesthetics. In addition, it is recommended for bronchial asthma (subcutaneously, orally, and also in the form of inhalation of a 2.5-5% solution), for urticaria and serum disease, and for hay fever (smearing the nose). The firm Boehringer releases it in ampoules of 0.06; intravenously 1, subcutaneously 1-2 ampoules. Tablets of 0.1 and 0.2 three times a day at 1/2, 1 or 2 tablets per dose and as a 10% solution at 15-30 drops per dose.