Penicillamine-d3 (Synonyms: D-Penicillamine-d3, β-Thiovaline-d3)

Penicillamine-d₃ is intended for use as an internal standard for the quantification of penicillamine by GC- or LC-MS. Penicillamine is an orally bioavailable copper chelator and penicillin degradation product.^1,2 It increases urinary and fecal copper excretion and decreases liver copper concentration in a rat model of copper overload when administered at 0.67 mmol/kg per day, but does not affect kidney, spleen, or brain copper levels.³ Penicillamine (100 mg/kg per day) dissolves copper-rich granules in hepatic lysosomes of Long-Evans cinnamon (LEC) rats, which spontaneously develop hepatic injury and acute hepatitis and have a mutation homologous to that of the human Wilson disease gene.⁴ Penicillamine has anticonvulsant and proconvulsant effects in mice when administered at 0.5 and 250 mg/kg, respectively, which are blocked by the nitric oxide synthase (NOS) inhibitors L-NAME and 7-nitroindazole .⁵ Formulations containing penicillamine have been used to treat Wilson disease, cystinuria, and active rheumatoid arthritis.

1.Delangle, P., and Mintz, E.Chelation therapy in Wilson's disease: From D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelatorsDalton Trans.41(21)6359-6370(2012) 2.Abraham, E.P., Chain, E., Baker, W., et al.Penicillamine, a characteristic degradation product of penicillinNature151(3821)107(1943) 3.Domingo, J.L., GÓmez, M., and Jones, M.M.Comparative efficacy of several potential treatments for copper mobilization in copper-overloaded ratsBiol. Trace Elem. Res.74(2)127-139(2000) 4.Klein, D., Lichtmannegger, J., Heinzmann, U., et al.Dissolution of copper-rich granules in hepatic lysosomes by D-penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon ratsJ. Hepatol.32(2)193-201(2000) 5.Rahimi, N., Sadeghzadeh, M., Javad-Paydar, M., et al.Effects of D-penicillamine on pentylenetetrazole-induced seizures in mice: involvement of nitric oxide/NMDA pathwaysEpilepsy Behav.3942-47(2014)