https://orcid.org/0000-0001-7635-783X
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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.
Abbreviations
| Aβ | = | amyloid-β- peptide |
| cAMP | = | cyclic adenosine monophosphate |
| CNS | = | central nervous system |
| COPD | = | chronic obstructive pulmonary disease |
| DNA | = | deoxyribonucleic acid |
| GABA | = | gamma-aminobutyric acid |
| HPLC | = | high-performance liquid chromatography |
| LD50 | = | median lethal dose |
| MAO | = | monoamine oxidase |
| PDE | = | phosphodiesterase |
| RNA | = | ribonucleic acid |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
JPM acknowledges the financial support to CESAM (UID/AMB/50017 – POCI-01-0145-FEDER-007638) by the Portuguese Foundation for Science and Technology (FCT; “Fundação para a Ciência e Tecnologia”), and FEDER (Fundo Europeu de Desenvolvimento Regional), within the Portugal 2020 Partnership Agreement and COMPETE 2020 (European Union). This work was also supported by the Portuguese ‘‘Fundação para a Ciência e a Tecnologia’’—FCT: MGA (SFRH/BPD/80451/2011), PFO (SFRH/BPD/108837/2015), and UMIB (Pest-OE/SAU/UI0215/2014) were co-funded by FEDER via Programa Operacional Fatores de Competitividade-COMPETE/QREN & FSE and POPH funds.