Pharmacological potential of methylxanthines: Retrospective analysis and future expectations

Abstract

Methylated xanthines (methylxanthines) are available from a significant number of different botanical species. They are ordinarily included in daily diet, in many extremely common beverages and foods. Caffeine, theophylline and theobromine are the main methylxanthines available from natural sources. The supposedly relatively low toxicity of methylxanthines, combined with the many beneficial effects that have been attributed to these compounds through time, generated a justified attention and a very prolific ground for dedicated scientific reports. Methylxanthines have been widely used as therapeutical tools, in an intriguing range of medicinal scopes. In fact, methylxanthines have been/were medically used as Central Nervous System stimulants, bronchodilators, coronary dilators, diuretics and anti-cancer adjuvant treatments. Other than these applications, methylxanthines have also been hinted to hold other beneficial health effects, namely regarding neurodegenerative diseases, cardioprotection, diabetes and fertility. However, it seems now consensual that toxicity concerns related to methylxanthine consumption and/or therapeutic use should not be dismissed. Taking all the knowledge and expectations on the potential of methylxanthines into account, we propose a systematic look at the past and future of methylxanthine pharmacologic applications, discussing all the promise and anticipating possible constraints. Anyways, methylxanthines will still substantiate considerable meaningful research and discussion for years to come.

An Insight into the Reactivity of the Electrogenerated Radical Cation of Caffeine

“…Beneficial health effects have been more recently proposed on obesity and diabetes, fertility, and neurodegenerative disease as Alzheimer's and Parkinson's disease; in these last cases the proper mechanism of caffeine-induced protection has not been fully clarified yet. Some detrimental effects also suggested an intrinsic complexity and concern due to the wide consumption [7]. A protective effect towards oxidative damage has been supported by in vitro and in vivo experiments [8][9][10], and a possible antioxidant ability of CAF has been studied [11,12], the role of CAF remaining nevertheless an open discussion.…”

Electrochemical Oxidation of Theophylline in Organic Solvents: HPLC‐PDA‐ESI‐MS/MS Analysis of the Oxidation Products

“…On the other hand, beneficial effects on human health have been ascribed to these compounds, depending also on their bioavailability and biotransformation in the organism, and the same are currently used as therapeutic tools. [1] Tea species are the main natural source of theophylline (TPh) that is also present in trace amounts in cocoa and coffee beans. Among the physiological mechanisms proposed for methylxanthines, TPh is thought acting mainly as antagonist of adenosine receptors and phosphodiesterase inhibitor.…”

A new insight into the oxidative mechanism of caffeine and related methylxanthines in aprotic medium: May caffeine be really considered as an antioxidant?

“…Among methylxanthines, caffeine (1,3,7-trimethylxanthine, CAF), theobromine (3,7-dimethylxanthine, TBr) and theophylline (1,3-dimethylxantine, TPh) are widely distributed in nature, where are present in almost one hundred species of the Plant Kingdom, including coffee, cacao (the major natural source of TBr) and tea (the major natural source of TPh) [1].…”

“…Many systemic effects in humans have been ascribed to methylxanthines, but mechanisms underlying their biological effects are not yet fully understood. Anyway, these relevant biological effects combined with a relatively low toxicity make these natural compounds pharmacological tools with increasing therapeutic potentialities [1].…”