Theobromine for treatment of uric acid stones and other diseases.

Theobromine (or 3,7-dimethylxanthine) is a natural alkaloid present in cocoa plant and its derivatives, such as chocolate. About 20% of ingested theobromine is excreted unchanged in the urine. Theobromine also derived from caffeine that is metabolized into theobromine by 12%. The primary metabolites of theobromine are 3-methylxantine, 7-methylxantine, 7-methyluric acid and 3,7-dimethyluric acid. Theobromine has an inhibitory activity of uric acid crystallization, because it has a structural pattern very similar to uric acid and can substitute uric acid molecules in the corresponding uric acid crystals, making them longer and thinner and decreasing their growth rate. Theobromine also favors the dissolution of crystals by decreasing supersaturation of uric acid by forming aggregates with uric acid through hydrogen bonds and aromatic stacking interactions (-stacking bonds) increasing urinary solubility of uric acid. Theobromine can be used for uric acid stone dissolution in combination with alkalinization to reduce the dose of citrate, thus preventing excessive alkalinization and the risk of formation of sodium urate crystals. Theobromine could also be used to treat patient with xanthine stones that cannot be dissolved by alkalinization because the solubility of xanthine is relatively independent of urinary pH. A metabolite of theobromine, 7-methylxanthine, has the potential to be used for the prevention of the formation of sodium urate crystals in the synovial fluid of gouty patients.