Benserazide-d3 is intended for use as an internal standard for the quantification of benserazide by GC- or LC-MS. Benserazide is a peripherally restricted inhibitor of aromatic L-amino acid decarboxylase (AADC; IC50 = 0.53 μM).1 It also inhibits tryptophan oxygenase and kynureninase (Kis = 41.8 and 26.4 μM, respectively, in rat liver homogenates), as well as hexokinase 2 (HK2), HK1, and HK4 (IC50s = 5.5, 25.1, and 40.5 μM, respectively, for the recombinant human enzymes).2,3 Benserazide (50-400 μM) is cytotoxic to SW480 colorectal cancer cells, an effect that can be reversed by HK2 siRNA knockdown, and inhibits proliferation of SW480, LoVo, HCT116, MCF-7, and SMMC-7721 cancer cells with IC50 values of 143, 151, 181.4, 186, and 210.4 nM, respectively.3 It reduces tumor growth in an SW480 mouse xenograft model when administered at doses of 300 and 600 mg/kg per day for 16 days. Oral administration of benserazide (8.8 mg/kg) inhibits AADC activity in rat liver, kidney, and brain by approximately 90, 90, and 25%, respectively, and increases striatal dopamine levels following administration of L-DOPA in rats. Benserazide (10 and 50 mg/kg) also inhibits striatal AADC and increases striatal dopamine levels following administration of L-DOPA in a 6-OHDA mouse model of Parkinson's disease.4
|1. Schultz, E. L-dopa as substrate for human duodenal catechol-O-methyltransferase and aromatic L-amino acid decarboxylase. Biomed. Chromatogr. 4(6), 242-244 (1990).|2. Bender, D.A. Inhibition in vitro of the enzymes of the oxidative pathway of tryptophan metabolism and of nicotinamide nucleotide synthesis by benserazide, carbidopa and isoniazid. Biochem. Pharmacol. 29(5), 707-712 (1980).|3. Li, W., Zheng, M., Wu, S., et al. Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2. J. Exp. Clin. Cancer Res. 36:58, (2017).|4. Shen, H., Kannari, K., Yamato, H., et al. Effects of benserazide on L-DOPA-derived extracellular dopamine levels and aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopamine-lesioned rats. Tohoku J.Exp.Med. 199(3), 149-159 (2003).