Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system (CNS) stimulant. It possesses a potency roughly equal to that of caffeine and is likely involved in the mediation of the effects of caffeine itself.
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||180.167 g·mol−1|
|Melting point||351 to 352 °C (664 to 666 °F; 624 to 625 K)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Production and metabolismEdit
Paraxanthine is not produced by plants and is only observed in nature as a metabolite of caffeine in animals. Paraxanthine is also a natural metabolite of caffeine in some species of bacteria. After intake, roughly 84% of caffeine is demethylated at the 3-position to yield paraxanthine, making it the chief metabolite of caffeine in the body.
Paraxanthine is also a major metabolite of caffeine in humans and other animals, such as mice. Shortly after ingestion, caffeine is metabolized into paraxanthine by hepatic cytochrome P450, which removes a methyl group from the N3 position of caffeine. After formation, paraxanthine can be broken down to 7-methylxanthine by demethylation of the N1 position, which is subsequently demethylated into xanthine or oxidized by CYP2A6 and CYP1A2 into 1,7-dimethylaric acid. In another pathway, paraxanthine is broken down into 5-acetylamino-6-formylamino-3-methyluracil through N-acetyl-transferase 2, which is then broken down into 5-acetylamino-6-amino-3-methyluracil by non-enzymatic decomposition. In yet another pathway, paraxanthine is metabolized CYPIA2 forming 1-methyl-xanthine, which can then be metabolized by xanthine oxidase to form 1-methyl-uric acid.
Certain proposed synthetic pathways of caffeine make use of paraxanthine as a bypass intermediate. However, its absence in plant alkaloid assays implies that these are infrequently, if ever, directly produced by plants.
Pharmacology and Physiological EffectsEdit
Paraxanthine is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNF-alpha and leukotriene synthesis, and reduces inflammation and innate immunity. Paraxanthine is a nonselective adenosine receptor antagonist which raises plasma epinephrine and diastolic blood pressure. Paraxanthine, unlike caffeine, acts as an enzymatic effector of Na+/K+ ATPase. As a result, it is responsible for increased transport of potassium ions into skeletal muscle tissue. Similarly, the compound also stimulates increases in calcium ion concentration in muscle.
Paraxanthine is believed to exhibit a lower toxicity than caffeine. While blood levels commensurate with average intake appear to be fairly innocuous, high blood concentrations of paraxanthine have been linked to miscarriage in pregnant mothers.
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- Media related to Paraxanthine at Wikimedia Commons