Choline

CHOLINE, hydroxide of trimethyloxyethylammonium, C₅H₁₅NO₂, is a quaternary ammonium base and in its structure is close to substances from the betaine group.

Choline is widely distributed in the animal and plant world, being present in tissues and body fluids as a component of lecithins, as well as in free form and in the form of its derivative - acetylcholine, (CH₃)₃N(OH)-CH₂-CH₂OCO-CH₃. In free form, it has been found in normal blood and in some nervous diseases, in muscles, adrenal glands, according to some authors, in cerebrospinal fluid in various diseases, e.g., in general paralysis, brain tumors, tabes, epilepsy, etc.; in urine after parathyroidectomy; Choline is also contained in milk and sweat; acetylcholine has been detected according to some indications in blood ('?), in uterine horns, etc.-Choline represents colorless crystals that easily absorb CO₂ and H₂O from the air; it has strongly expressed alkaline properties; with HCl it gives chlorhydrate C₅H₁₄NOCl; with AuCl₃ it gives needle-shaped crystals of composition C₅H₁₄NOCl AuCl₃, insoluble in cold water and alcohol; with corrosive sublimate it gives a compound C₅H₁₄NOCl 6HgCl₂; chloroplatinate (C₅H₁₄NOCl)₂PtCl₄, crystallizing dimorphically (in rhombic and monoclinic systems), which can serve for its identification. For

the detection of Choline, its periodide (see Florence test) is also used, which forms when a solution of I in KI is added to a not too diluted weakly acidic or weakly alkaline (from the addition of soda) solution of Choline, and which under the microscope has the form of needles, rhomboid plates, etc. Choline is precipitated by almost all alkaloid reagents. The physiological significance of Choline is still very little elucidated. It is a component of lecithins and sphingomyelins, free Choline apparently has an effect on the circulatory system opposite to that of adrenaline, enhances peristalsis of the small intestines; to an even greater extent, acetylcholine has this same effect. The latter is attributed an important role in muscle contraction, namely the role of a factor causing and maintaining tonic contractions of skeletal musculature (Gellhorn, Northup). Acetylcholine also has an exciting effect on the cardiac muscle, which is why it is identified with "Vagusstoff" of Loewi (O. Loewi). Choline, administered orally, is relatively non-toxic; however, its parenteral administration into the blood or under the skin is accompanied by severe symptoms. A strongly toxic effect is possessed by the unsaturated Choline compound neurin (see). Very little is also known about the formation of Choline in the body and its changes. Its nitrogen is apparently excreted in the form of ammonia with urine. There are indications that Choline is formed from the amino acid serine by its methylation and subsequent decarboxylation. There are indications of a connection between Choline and the formation of creatine in the body. M. Kalyagina. The pharmacological action of Choline is basically determined by its chemical closeness to muscarine (see) and its exciting effect on the parasympathetic system: from Choline the heartbeat slows down, the pupil narrows, the secretion of gastric juice increases; peristalsis of the intestines is enhanced due to excitation of Auerbach's plexus. Zuelzer and Le Heux consider Choline even a specific hormone for intestinal peristalsis, not identifying (Zuelzer) however Choline with the hormone (now neo-hormonal) - the protein-free extract from fresh cow spleen (Schering), as some authors do. From Choline the vessels dilate and blood pressure decreases; thus Choline is an antagonist of adrenaline; it is interesting that vessels dilated by Choline narrow not only from adrenaline but also from atropine. More strongly acting than choline is acetylcholine, introduced into medicine in 1926, stimulating all parasympathetic nerve endings; its influence on the heart and on organs with smooth musculature is especially pronounced; therefore, if acetylcholine is formed in the intestines, the strongest diarrhea may occur. Under the influence of acetylcholine, the secretion of adrenaline is enhanced. The action of choline-muscarine in general is very similar to the action of mushroom muscarine (Fuhner), but the lethal doses for warm-blooded animals are higher than for mushroom muscarine. The local effect on the pupil of choline-muscarine is also weaker than from mushroom muscarine. Choline-muscarine has a curare-like action (Boehm). Honda asserts that choline-muscarine is 5 times weaker than curarine. Choline-muscarine is excreted with urine. Choline can play a prominent role in the treatment of relaxations and paralyzes of the gastrointestinal peristalsis that often occur after operations on the intestine; the combination of Choline with physostigmine in these cases is especially successful; Choline is also recommended for functional atonies of the stomach and intestines, for nervous dyspepsia; for vascular hypertensions to lower blood pressure; in the climacteric period in women to accelerate the involution of the ovaries. As a medicinal preparation, Cholinum chloratum medicinale is used, produced by Merck in ampoules containing 0.6 Choline; the contents of the ampoule are dissolved in 240 cm³ of physiological solution and injected very slowly into the vein with the calculation to introduce Choline at 0.01 per 1 kg of weight.