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Alkylxanthines as research tools.

J W Daly1

  • 1Section on Pharmacodynamics, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Journal of the Autonomic Nervous System
|June 28, 2000
PubMed
Summary
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Caffeine and related xanthines impact cellular functions by blocking adenosine receptors and inhibiting phosphodiesterases. While caffeine is preferred for calcium release, other xanthines offer greater potency and selectivity for these targets.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cell Physiology

Background:

  • Caffeine, a methylxanthine, exerts pharmacological effects primarily through adenosine receptor blockade, phosphodiesterase inhibition, and modulation of intracellular calcium release.
  • Various xanthine derivatives have been synthesized to target specific cellular mechanisms.

Purpose of the Study:

  • To review the pharmacological actions of caffeine and related xanthines.
  • To highlight the development of selective adenosine receptor antagonists and phosphodiesterase inhibitors.
  • To discuss the role of caffeine in activating intracellular calcium release channels.

Main Methods:

  • Literature review of pharmacological studies on methylxanthines.
  • Analysis of structure-activity relationships for xanthine derivatives.

Related Experiment Videos

  • Examination of data on receptor antagonism and enzyme inhibition.
  • Assessment of caffeine's effects on intracellular calcium dynamics.

    • Main Results:

    • Caffeine's effects are linked to adenosine receptor antagonism, phosphodiesterase inhibition, and calcium release.
    • Potent and selective adenosine receptor antagonists have been developed.
    • More potent and selective phosphodiesterase inhibitors than caffeine or theophylline exist.
    • Caffeine is a preferred agent for activating calcium release channels, though high concentrations are needed.

    Conclusions:

    • Xanthine derivatives offer diverse pharmacological profiles with varying potencies and selectivities.
    • Development of specific xanthine-based compounds allows for targeted modulation of cellular signaling pathways.
    • Caffeine's utility in calcium signaling is established, but its non-specific effects at high concentrations warrant consideration.