Caffeine pharmacological properties

Theobromine (3,7-dimethylxanthine, 3,7-dihydro-3,7-dimethyl-lW-purine-2,6-dione). C7H,N402, Mr 180.17 formula, see under theophylline. Monoclinic, bitter tasting needles, mp. 357 °C, sublimes at 290-295 °C, soluble in hot water, alkali hydroxides, concentrated acids, moderately soluble in ammonia, poorly soluble in cold water and alcohol. With acids T. forms salts which decompose in water detection by the murexid reaction. T. is the main alkaloid of cocoa (Theobroma cacao, 1.5-3 wt.-%), from which it is obtained - especially from the husks in which it accumulates during fermentation. The typical bitter taste of cocoa is the result of interactions between T. and the pip-erazinediones formed in the roasting process. T. has diuretic, vasodilatory, and stimulating effects on cardiac muscle. The activities are weaker than those of the structurally related caffeine (a methylation product of T.) with which it co-occurs in cola nuts. For further pharmacological properties, see table under theophylline. 

C7H8N4O2, Mr 180.17, thin, bitter-tasting platelets, mp. 270-274 °C (monohydrate), moderately soluble in water, very soluble in hot water, alkali hydroxides, ammonia, dilute acids. A purine alkaloid from the leaves of the tea plant, also contained in matd (Ilex paragua-riensis and Paullinia cupana). The methylxanthines T., caffein(e), and theobromine are among the oldest known stimulants and drugs. Their pharmacological properties are compared in the table. In high doses T. can cause epilepsy-like convulsions. T. also exhibits antiasthmatic activity. ... 

Table Pharmacological properties of Theophylline, compared to Caffeine and Theobromine.

Documented effects The biological activity is due to the presence of saponins, and removal of the saponins from the tincture leads to complete loss of the pharmacological properties (Ivanova 1963). The sedative effect of this species is nearly twice as strong as that of Valeriana (Tolmachev 1976). The roots of this species reduce excitability of the nervous system. Clinical tests showed that application of an alcohol infusion stopped or noticeably reduced chest pain as well as nervous and cardiovascular excitation caused by hypodermic introduction of caffeine (Akopov 1990). 

Xanthine derivatives have a number of pharmacological properties in common. Five major actions are observed (1) central nervous system and respiratory stimulation, (2) skeletal muscle stimulation, (3) diuresis, (4) cardiac stimulation, and (5) smooth-muscle relaxation. Caffeine (29) increases central nervous system activity and its main effect is on the cerebral cortex, where it acts to produce clear thought and reduce drowsiness and fatigue. The normal dose is 100-200 mg (Cordell, 1981). The oral LD50 in mouse is 127-137 mg/kg the oral LD50 in rat for theobromine (31) is 950... 

Caffeine, the most commonly known constituent of tea, has diuretic and CNS-stimulant activities, as well as numerous other kinds of pharmacological properties (see coffee). 

Because the physiological and pharmacological properties of caffeine represent the cumulative effects of not only the parent compound but also its metabolites, it is quite possible that effects attributed to caffeine per se are in fact mediated by one or more of its metabolites. It must also be noted that most of the knowledge about caffeine s effects has been derived from acute administration to fasted subjects submitted to a period of caffeine abstinence in order to ensure low plasma caffeine concentrations. It is thus difficult to extrapolate the results to the usual pattern of caffeine consumption in which... 

The physiological and pharmacological properties of caffeine cannot be explained by a single biochemical mechanism. Three principal hypotheses have been investigated to explain the diverse actions of caffeine. 

Many pharmacologically active organic chemicals fonnd in natnre are alkaloids. In general, these componnds contain one or more nitrogen atoms, which in turn impart some basicity to the molecnle. Well-known alkaloid examples are caffeine, cocaine, codeine, ephedrine, morphine, nicotine, qninine, and scopolamine. Heroin is derived from morphine by a chemical modification that increases lipophilicity, making the heroin molecnle inherently more pharmacologically potent than morphine. The exhibition of its basic properties by an alkaloid (Aik) involves (by definition) the acceptance of a proton H+ according to ... 

Griffiths, R. R., Woodson, D. P. (1988b). Reinforcing properties of caffeine Studies in human and laboratory animals. Pharmacology, Biochemistry, and Behavior, 28, 419-427. 

Theobromine, the major alkaloid in cocoa, has similar pharmacological activities as caffeine. However, its stimulant activities on the central nervous system, respiration, and skeletal muscles are much weaker than those of caffeine, but its cardiac stimulant, coronary dilating, smooth muscle relaxant, and diuretic properties are stronger (Goodman and oilman). 

Methylated xanthines have pharmacologic applications (theophylline = 1,3-di-methylxanthine, caffeine = 1,3,7-trimethylxanthine). Certain analogs of the purines (8-azaguanine, 6-mercaptopurine) have antibiotic and cytostatic properties they have been used as chemotherapeutic agents against tumors. 

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