Paraxanthine-d6 (Synonyms: 1,7-Dimethylxanthine-d6)

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 (K_is = 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)