Amiodarone-d4 is intended for use as an internal standard for the quantification of amiodarone by GC- or LC-MS. Amiodarone is a class III antiarrhythmic agent, in that it prolongs both cardiac action potential and refractoriness by blocking potassium currents.1 It inhibits the voltage-gated potassium channel hERG, also known as KCNH2, with an IC50 value of 1 µM.2 In addition, amiodarone binds with high affinity to the sigma-1 opioid receptor, 3-β-hydroxysteroid δ8δ7 isomerase, and C-8 sterol isomerase (Kis = 1, 25, and 62 nM, respectively) and inhibits human thyroid hormone receptors α and β (IC50s = 0.6 and 0.65 µM, respectively).3,4 It also inhibits the cytochrome P450 (CYP) isoforms CYP2C8 and CYP3A4 in vitro at low micromolar concentrations.5
1.Campbell, T.J., and Williams, K.M.Therapeutic drug monitoring: Antiarrhythmic drugsBr. J. Clin. Pharmacol.52307-319(1998) 2.Sinha, N., and Sen, S.Predicting hERG activities of compounds from their 3D structures: Development and evaluation of a global descriptors based QSAR modelEur. J. Med. Chem.46(2)618-630(2011) 3.Laggner, C., Schieferer, C., Fiechtner, B., et al.Discovery of high-affinity ligands of σ1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screeningJ. Med Chem.48(15)4754-4764(2005) 4.Carlsson, B., Singh, B.N., Temciuc, M., et al.Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodaroneJournal of Medicinal Chemistry45(3)623-630(2002) 5.Polasek, T.M., Elliott, D.J., Lewis, B.C., et al.Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitroJ. Pharmacol. Exp. Ther.311(3)996-1007(2004)