Xanthine derivatives in the heart: blessed or cursed?

Area of Science:

• Pharmacology
• Cardiology
• Molecular Biology

Background:

• Methylxanthines (e.g., theophylline, caffeine) are widely used for cardiorespiratory disorders and as psychoactive agents.
• Research is ongoing into the cardiac actions of xanthine derivatives due to their global consumption and synthesis of new compounds.

Purpose of the Study:

• To review the molecular mechanisms of xanthine derivatives, focusing on their adenosine receptor antagonism.
• To overview studies on xanthine effects on cardiac impulse, conduction, and myocardial activity.
• To discuss beneficial and harmful actions of methylxanthines, including adenosine receptor subtype-specific antagonists.

Main Methods:

• Review of basic and human studies on methylxanthine actions.
• Analysis of electrophysiological and mechanical effects on the working myocardium.
• Examination of pharmacological features and clinical observations of adenosine receptor antagonists.

Main Results:

• Xanthine derivatives may inhibit cardioprotective adenosine effects by antagonizing adenosine receptors (A(1), A(2A), A(2B), A(3)).
• Acute caffeine/theophylline administration inhibits preconditioning in humans; long-term effects in humans are unstudied.
• Long-term methylxanthine treatment can upregulate adenosine receptors and increase blood adenosine levels.

Conclusions:

• Xanthine derivatives' adenosine receptor antagonism impacts cardiac function, potentially counteracting endogenous adenosine's protective roles.
• Further research is needed on long-term methylxanthine administration effects in humans.
• Novel xanthine derivatives with higher receptor specificity, optimal solubility, and reduced side effects are desirable.