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Theobromine-d6 is intended for use as an internal standard for the quantification of theobromine by GC- or LC-MS. Theobromine is a methylxanthine alkaloid and derivative of caffeine that has been found in cocoa beans and has diverse biological activities.1,2,3 It is an adenosine A1 receptor antagonist (IC50s = 200-280 μM in radioligand binding assays using rat brain membranes).2 Theobromine (150 μg/ml) increases AMPK phosphorylation and inhibits adipocyte differentiation, ERK and JNK phosphorylation, and IL-6 and TNF-α production in 3T3-L1 preadipocytes cultured in differentiation medium.1 It inhibits decreases in renal cortex SIRT1 activity and increases in NADPH oxidase-dependent reactive oxygen species (ROS) production, as well as reduces kidney hypertrophy and albuminuria in a spontaneously hypertensive rat model of streptozotocin-induced diabetes when administered at a dose of 5 mg/kg per day.3 Theobromine is toxic to dogs with an LD50 value of 250 to 500 mg/kg.4

1.Jang, Y.J., Koo, H.J., Sohn, E.-H., et al.Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathwaysFood Funct.6(7)2365-2374(2015) 2.Daly, J.W., Butts-Lamb, P., and Padgett, W.Subclasses of adenosine receptors in the central nervous system: Interaction with caffeine and related methylxanthinesCell. Mol. Neurobiol.3(1)69-80(1983) 3.Papadimitriou, A., Silva, K.C., Peixoto, E.B.M.I., et al.Theobromine increases NAD?/Sirt-1 activity and protects the kidney under diabetic conditionsAm. J. Physiol. Renal Physiol.308(3)F209-F225(2015) 4.Lawrence, L.P.Chocolate toxicosisThe 5-minute veterinary consult: Canine and feline(2004)

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