One may wonder why methylxanthines are so abundant in beverages used by humans for centuries, or in cola-drinks that have been heavily consumed since their appearance. It is likely that humans have stuck to any brew containing compounds with psychoactive properties, resulting in a better daily life, i.e., more efficient thinking, exploring, hunting, etc., however, without the serious side effects of drugs of abuse. The physiological effects of methylxanthines have been known for a long time and they are mainly mediated by the so-called adenosine receptors. Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food. The consequences of adenosine receptor blockade by natural compounds present in cacao/chocolate are here reviewed. Palatability and health benefits of methylxanthines, in general, and theobromine, in particular, have further contributed to sustain one of the most innocuous and pleasant habits: chocolate consumption.

Cocoa consumption began in America and in the mid sixteenth Century it quickly spread to Europe. Beyond being considered a pleasant habit due to its rich sweet lingering taste, chocolate was considered a good nutrient and even a medicine. Traditionally, health benefits of cocoa have been related with the high content of antioxidants of Theobroma cocoa beans. However, the direct psychoactive effect due to methylxanthines in cocoa is notable. Theobromine and caffeine, in the proportions found in cocoa, are responsible for the liking of the food/beverage. These compounds influence in a positive way our moods and our state of alertness. Theobromine, which is found in higher amounts than caffeine, seems to be behind several effects attributed to cocoa intake. The main mechanisms of action are inhibition of phosphodiesterases and blockade of adenosine receptors. Further mechanisms are being explored to better understand the health benefits associated to theobromine consumption. Unlike what happens in other mammals -pets- included, theobromine is safe for humans and has fewer unwanted effects than caffeine. Therefore, theobromine deserves attention as one of the most attractive molecules in cocoa.

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Caffeine, theophylline and theobromine are the most known methylxanthines as they are present in coffee, tea and/or chocolate. In the last decades, a huge experimental effort has been devoted to get insight into the variety of actions that these compounds exert in humans. From such knowledge it is known that methylxanthines have a great potential in prevention, therapy and/or management of a variety of diseases. The benefits of methylxanthine-based therapies in the apnea of prematurity and their translational potential in pediatric affections of the respiratory tract are here presented.

Methylxanthines (MTXs) are consumed by almost everybody in almost every area of the world. Caffeine, theophylline and theobromine are the most well-known members of this family of compounds; they are present, inter alia, in coffee, tea, cacao, yerba mate and cola drinks. MTXs are readily absorbed in the gastrointestinal tract and are able to penetrate into the central nervous system, where they exert significant psychostimulant actions, which are more evident in acute intake. Coffee has been paradigmatic, as its use was forbidden in many diseases, however, this negative view has radically changed; evidence shows that MTXs display health benefits in diseases involving cell death in the nervous system. This paper reviews data that appraise the preventive and even therapeutic potential of MTXs in a variety of neurodegenerative diseases. Future perspectives include the use of MTXs to advance the understanding the pathophysiology of, inter alia, Alzheimer's disease (AD) and Parkinson's disease (PD), and the use of the methylxanthine chemical moiety as a basis for the development of new and more efficacious drugs.