LOBELIA

LOBELIA, Lobelia inflata (inflated lobelia), a plant of the Campanulaceae-Lobelioidae family (Indian tobacco), grows wild or is cultivated in the eastern part of North America; in Western Europe it began to be intensively cultivated after the imperialist war; used by natives as a tobacco substitute. The stem is branching, up to 60 cm in height, leaves are simple, variable; covered with hairs on both sides, especially along the nerves and at the edges; edges are serrated. The inflorescence is racemose; flowers are whitish or light blue; corolla is two-lipped. Five stamens, fused in the upper part. Ovary is inferior. Fruit is a dehiscent capsule. Seeds are brown, oblong, 0.5-0.7 mm in length. The aerial parts of the plant are collected at the end of flowering and sold in the form of compressed small bricks containing pieces of stems and leaves mixed with flowers and fruits. The active principle of L. is the alkaloid lobeline. This name was formerly applied to the substance isolated by Dreser, which was a mixture of differently acting principles of lobelia and represented a yellowish, honey-like mass. The sulfate salts of this mixture of alkaloids in the form of a yellowish amorphous powder were sold under the name Lobelinum sulfuricum; this preparation, which has retained its name to the present day in contrast to chemically pure lobeline, was taken internally instead of Tincturae Lobeliae. In 1915, T. Wieland (Heinrich Wieland) isolated crystalline alpha-Lobelin, which is the main active principle of L. At present, up to 10 separate alkaloids have been isolated from L., most of which are chemically similar to lobeline; in the plant these alkaloids are combined with lobelic acid. In the milky juice of L. there is the glycoside Lobelacrin, as well as essential oil and resin. The hydrochloride salt of alpha-Lobelin, Lobelinum hydrochloricum, sold by the firm Boehringer Sohn under the name Lobelin-Ingelheim, is a white crystalline powder, soluble in 40 parts water, 10 parts alcohol and very soluble in chloroform. Melting point is 118-120°. When boiled, the aqueous solution of lobeline decomposes with the elimination of acetophenone and the appearance of the characteristic odor of the latter. Alpha-lobelin is a derivative of piperidine; at present it has been synthesized and has the following structural formula: CH2CH2, C6H6CO, CH2CH2, CH2CH2CH2OH, C5H5N-CH3. Natural lobeline rotates the plane of polarization to the left. In L. there is also a racemic form, named lobelidine; it is pharmacologically twice as weak as the levorotatory isomer. Being a derivative of piperidine, lobeline is close to nicotine and coniine both in chemical structure and pharmacological properties. The distinctive feature of lobeline is its highly selective action on the respiratory center. The excitation of respiration observed when injecting lobeline is due to both deepening and its acceleration, with deepening of respiration occurring first, and then together with acceleration it becomes more superficial. After subcutaneous administration to humans of a therapeutic dose of lobeline (0.01), the increase in lung ventilation reaches its maximum in 10-45 minutes and can continue for 30-35 minutes; at the same time, the excitability of the respiratory center to CO2 increases, and its tension in the alveolar air decreases. Lobeline also causes an increase in gas exchange; absorption of O2 and excretion of CO2 increases. The respiratory coefficient in experiments on healthy subjects increases. However, this change in gas exchange is short-lived; excitation of respiration remains for some time after the return of gas exchange to normal. The stimulating effect of lobeline on the respiratory center is also manifested when the latter is depressed by various poisons. Lobeline has a particularly pronounced effect in morphine poisoning; its effect on the respiratory center poisoned by chloral hydrate and chloroform is less pronounced. Intravenous administration of lobeline has an even stronger and faster effect; but with this, as a rule, especially with rapid injection of large doses, a brief arrest of respiration precedes the excitation; it usually lasts only a few seconds, but in some cases half a minute or longer. Wieland explains this arrest by the excitation of the center of the vagus nerve, which occurs with rapid administration of lobeline; with slow intravenous injection, such a delay is not observed. With repeated administration of lobeline, there is neither weakening of its effect on the respiratory center nor the phenomenon of cumulation. Along with the respiratory center, especially when large doses of lobeline are used, other bulbar centers are also excited. The excitation of the center of the cardiac vagi that occurs with intravenous administration of lobeline leads to a noticeable slowing of the heartbeat and lowering of blood pressure; this lowering of blood pressure is quickly followed by an increase due to vasoconstriction. The vasoconstriction caused by lobeline, as in the action of nicotine, is explained mainly by the excitation of sympathetic ganglia. Like nicotine and other ganglionic poisons, lobeline also has a selective stimulating effect on the adrenal medulla and with its resorptive action significantly increases the secretion of adrenaline. Due to the observed hyperadrenalinemia, the symptoms of the direct action of lobeline are joined by an adrenaline effect. It is responsible for the significant hyperglycemia observed after administration of lobeline. After extirpation of the adrenal glands, lobeline does not cause hyperglycemia. The direct action of lobeline on smooth muscles and vessels is insignificant. The cardiac muscle and motor nodes of the heart are depressed by lobeline after a preliminary brief excitation. Intravenous administration of toxic doses of lobeline (several mg per 1 kg of weight) in animals causes vomiting, tonic-clonic convulsions of cerebral origin and depression of respiration, following the primary arrest and excitation of it. Preparations and their application: Herba Lobeliae; internally up to 0.1 per dose. Tinctura Lobeliae; internally 20 drops 3-4 times a day; highest single dose - 1.0. Both preparations were formerly used in bronchial asthma, whooping cough and bronchitis. At present they are little used. Lobelinum hydrochloricum; in ampoules of 0.01 and 0.003. For adults subcutaneously and intramuscularly 0.01 with signs of respiratory weakness during infectious diseases, especially pneumonia, measles and diphtheria, as well as in acute poisoning with morphine, carbon monoxide, illuminating gas, scopolamine, narcotic fats of the fatty series, hydrocyanic acid and other poisons that paralyze the respiratory center. If an immediate effect is needed, 0.003 is administered intravenously (slow administration!). Cases are described where lobeline succeeded in restoring respiration when other means had completely failed. Injections of lobeline can be repeated many times. Lobeline (0.003 subcutaneously) is widely used as a means of restoring respiration in asphyxia of newborns. Great hopes are placed on Lobelinum hydrochloricum as an antidote in cases of poisoning with CO. Lit.: Antal L., Pharmacological investigations on lobeline. (Lobelin-Ingelheim), Arch. f. experim. Pathol. u. Pharmakol., Vol. CXV, 1926; Bertram F., Zur Pharmakologie des Lobelins, ibid., Vol. CXXVIII, 1928; Marschall W., Alpha lobelin as respiratory stimulant, Arch. int. med., v. XLII, 1928; Sakussow W., Ueber die Wirkung des Lobelins auf den Blutzirkulationsapparat, Archiv fur experimentelle Pathologie und Pharmakologie, Band CXXXIII, 1928; Schoen R. und Kaibisch N., Die Wirkung zentral erregender Mittel auf den respiratorischen Stoffwechsel, Deutsches Archiv fuer klinische Medizin, Band CL, 1926; Wieland H. und Mayer R., Pharmakologische Untersuchungen am Atemzentrum, Archiv fuer experimentelle Pathologie und Pharmakologie, Band XCII, 1921. O. Anichkov.