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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Sympathomimetic effects of paraxanthine and caffeine in humans.

Caffeine is metabolized extensively (on average 80%) to paraxanthine. With regular caffeine consumption, average serum levels of paraxanthine are two thirds those of caffeine. Both caffeine and paraxanthine competitively and nonselectively inhibit adenosine receptors in vitro. To examine the contribution of paraxanthine to the pharmacologic activity of caffeine, we administered to 12 subjects in a crossover design oral caffeine (2 or 4 mg/kg) versus placebo or oral paraxanthine (same dose as caffeine) versus placebo, each after 3 days of methylxanthine abstinence. Both caffeine and paraxanthine significantly increased diastolic blood pressure, plasma epinephrine levels, and free fatty acids. Caffeine and paraxanthine produced a similar magnitude of response at 4 mg/kg; however, caffeine appeared to produce greater responses than paraxanthine at 2 mg/kg. Caffeine and paraxanthine have similar sympathomimetic actions. The activity of paraxanthine needs to be considered in understanding the clinical pharmacology of caffeine, particularly with chronic, repetitive caffeine consumption.[1]


  1. Sympathomimetic effects of paraxanthine and caffeine in humans. Benowitz, N.L., Jacob, P., Mayan, H., Denaro, C. Clin. Pharmacol. Ther. (1995) [Pubmed]
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