Paraxanthine-d6 is intended for use as an internal standard for the quantification of paraxanthine by GC- or LC-MS. Paraxanthine is an active metabolite of caffeine .1 It is formed via N3-demethylation of caffeine by the cytochrome P450 (CYP) isoform CYP1A2. Paraxanthine is an adenosine A1 and A2 receptor antagonist (Kis = 35 and 22 µM, respectively).2 In vivo, paraxanthine (30 mg/kg) increases striatal cGMP and extracellular striatal dopamine levels and locomotor activity, as well as inhibits motor depression induced by the adenosine A1 agonist CPA or the adenosine A2 receptor agonist CGS 21680 in rats not habituated to caffeine.3 It also promotes wakefulness and increases locomotor activity and core temperature in narcoleptic transgenic mice without increasing behavioral anxiety.4
1.Tassaneeyakul, W., Birkett, D.J., McManus, M.E., et al.Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoformsBiochem. Pharmacol.47(10)1767-1776(1994) 2.Chou, C.-C., and Vickroy, T.W.Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissuesAm. J. Vet. Res.64(2)216-224(2003) 3.OrrÚ, M., Guitart, X., Karcz-Kubicha, M., et al.Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humansNeuropharmacology67476-484(2013) 4.Okuro, M., Fujiki, N., Kotorii, N., et al.Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic miceSleep33(7)930-942(2010)