Theobromine

THEOBROMINE (C7H8N4O2), Theobrominum, 3,7-dimethylxanthine; 3,7-dimethyl-2,6-dioxypurine, NH-CO-N=C-N(CH3)-C=O, C7H8N4O2, an alkaloid; colorless, microscopic needles, bitter taste. Slightly soluble in water, alcohol, and ether, soluble in alkalis; melts at 351°. First obtained by Voskresensky from the seeds of the cocoa tree Theobroma cacao (see Cocoa). In cocoa powder, T. is contained in amounts of 0.08-2%; it is also found in kola nuts (Cola acuminata - about 0.02%), in guarana paste (Pasta Guarana), made by natives in Brazil from seeds of Paullinia guaranae, s. sorbilis and coca seeds; in very small quantities it is found in tea leaves. Also obtained synthetically. A qualitative test for T. is the appearance of yellow or reddish spots after evaporating to dryness a mixture of 0.2 g T. and 2 cm³ hydrochloric acid and a crystal of potassium chlorate; moistened with ammonia solution, these spots turn purple. Pharmacologically, T. belongs to the caffeine group and is in many respects similar to the latter. The differences are as follows: T. hardly stimulates the central nervous system, for which reason T. cannot eliminate fatigue and significantly increase performance for a long time; on the isolated heart it acts stronger than caffeine (see Diuretin); the diuretic effect of T. is more constant and prolonged, since with its weak action on vascular centers T. has a more pronounced direct vasodilating effect; the mechanism of T.'s diuretic influence is the same as that of caffeine (see Diuretics); in addition to renal, T. strongly dilates coronary and cerebral vessels. The simultaneous administration of alkalis inhibits, while the intake of acids enhances theobromine diuresis. After taking T., especially in large doses, patients sometimes complain of unpleasant sensations in the stomach, nausea, vomiting, loss of appetite, headache. Theobromine is excreted from the body through the kidneys partly unchanged, mainly in the form of monomethylxanthine. Application. 1. As a diuretic for edema, mainly of cardiac origin; in heart diseases T. is often combined with cardiac glycoside preparations; usually small doses (0.25-0.5) are prescribed 2 times a day, gradually increasing up to 8 times pro die; during long-term treatment, intervals are established. 2. For angina pectoris, cardiac asthma, renal sclerosis and hypertensions, with spasm of cerebral vessels (migraine, headache, neuralgia) often in combination with antipyretics. In these cases, T. enjoys a reputation as a vasodilating prophylactic and therapeutic agent; during a vascular attack, T. is useless due to the slowness of absorption. 3. To enhance the excretion of poisons and toxins from tissues when they are in a dissolved state in body fluids. 4. Bronchial asthma is also an indication for the use of T. due to its relaxation of the smooth muscle tone. Preparations. 1. Theobrominum purum, a white, poorly soluble powder; per os - 0.5 (3.0-5.0). 2. Diuretin (see). 3. Agurin (see). 4. Theacylon (Merck), theobromine acetylsalicylate, neutral reacting, not changing in the stomach and breaking down in the intestine, poorly soluble in water, tasteless powder; as a diuretic 0.3-0.5; intestinal disturbances are rare, transient albuminuria is sometimes observed; therefore caution is needed in kidney disease; cases of toxic effects on the liver have been described. 5. Aliyltheobrominum, allyltheobromine, a synthetic preparation, available as a 1% solution with 2% lithium benzoate for intramuscular injections of 0.02-0.06. Poisoning (acute) more often occurs from soluble salts of T. and is characterized by disturbances of the digestive tract, nausea, vomiting; after large doses, muscle tremors, increased reflexes, convulsions, phenomena of central nervous system excitation are common; cases of kidney irritation, erythema, necrosis of renal parenchyma have been described. Treatment consists of washing the stomach, in circulatory disorders - nitrites and warmth. Household poisoning (chronic) with theobromine is manifested by impaired digestion, tremors, palpitations, insomnia and nervousness.

A. Kuznetsov. THEOPHYLLINE, Theophyllinum, 1,3-dimethyl-xanthine; 1,3-dimethyl-2,6-dioxypurine, isomer of theobromine (see), C7H8N4O2, a powder poorly soluble in water, melting at 264°, N(CH3)-CO-N=C-N(CH3)-C=O

I

CO

>CH N(CH3)-C-------N^ Found in tea leaves (Kossel) in small quantities, difficult to isolate, therefore expensive and rarely used in medical practice. The strongest diuretic among purine derivatives (2 times stronger than theobromine), acts quickly but not for long. On the central nervous system it has an exciting effect, but weaker than caffeine; on the heart it has negligible influence; the local dilating effect on vessels is very pronounced. After taking T., headache, digestive disorders, vomiting and diarrhea are often observed, sometimes epileptiform convulsions. Excreted from the body by the kidneys unchanged and in the form of monomethylxanthine; sometimes symptoms of kidney parenchyma damage appear; maximum dose pro die 1.0; a case of fatal poisoning from a dose of 1.6 has been described; it is recommended not to exceed the daily dose of 0.8, to take for no more than one day, alternating with theobromine. Application: 1. For angina pectoris, cardiac asthma, for renal sclerosis, for hypertension - as a vasodilating agent. 2. For edema and other forms of water retention in the body. Theophylline is usually used in these cases after unsuccessful or little favorable effects of cardiac and dietary measures; treatment is started with small doses (0.1-0.2), which are more active than large ones; the latter sometimes give an opposite, anti-diuretic effect; this latter sometimes occurs in diabetes insipidus and after repeated administration of small doses; therefore it is desirable to have breaks in treatment; small doses are gradually increased from 1-2 times to 4 times a day. In acute nephritis, it is recommended to refrain from using theophylline, as under its influence hematuria may increase. In the terminal uremic stage in kidney disease, T. is useless. Due to the high cost of T., it is replaced by the synthetic preparation theocin (Theocinum) - a crystalline powder soluble in water 1:180. Preparations. 1. Theophyllinum (Theocinum), a colorless powder, dose 0.2-0.5; highest dose 0.5 (1.5). 2. Theophyllinum (Theocinum) natrio-aceticum - sodium acetic T., colorless crystals; dose 0.3-0.5 three times a day; soluble in water, given after meals; highest dose 1.5 pro die. 3. Euphyllinum, euphylline (see). - Poisonings from T. are often of a medical nature. In an amount of 0.5, it causes restlessness and convulsive phenomena, albuminuria and hemoglobinuria; the prognosis is favorable. Treatment - stomach lavage; in circulatory disorders - warm baths, amyl nitrite, nitroglycerin." Lit.: Bliss A. a. Morrison R., Comparative study of certain xanthane diuretics, Jour. Tennessee med. as., V. XXV, 1932; F r h l i c h A. u. Z a k' E., Experimental Beitrag zur Kenntnis des Theophyllins, Klin. Wochenschr., B. IV, 1925.