Tolcapone-d4 is intended for use as an internal standard for the quantification of tolcapone by GC- or LC-MS. Tolcapone is a reversible inhibitor of catechol-O-methyltransferase (COMT; Ki = 0.27 nM for human recombinant COMT), an enzyme that degrades catecholamines, including dopamine and L-DOPA .1,2 Tolcapone crosses the blood brain barrier and can inhibit both peripheral and central COMT activity.3,4 By inhibiting COMT, tolcapone increases L-DOPA efficacy and reduces L-DOPA-induced motor complications in animal models of Parkinson's disease.3
|1. Lotta, T., Vidgren, J., Tilgmann, C., et al. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: A revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34(13), 4202-4210 (1995).|2. M•nnist•, P.T., and Kaakkola, S. Catechol-O-methyltransferase (COMT): Biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol. Rev. 51(4), 593-628 (1999).|3. Espinoza, S., ManagÓ, F., Leo, D., et al. Role of catechol-O-methyltransferase (COMT)-dependent processes in Parkinson's disease and L-DOPA treatment. CNS Neurol. Disord. Drug Targets 11(3), 251-263 (2012).|4. M•nnist•, P.T., Tuomainen, P., and Tuominen, R.K. Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat. Br. J. Pharmacol. 105(3), 569-574 (1992).