[2H3]-Quinidine

Description

Quinidine-d₃ is intended for use as an internal standard for the quantification of quinidine by GC- or LC-MS. Quinidine is a stereoisomer of the antimalarial agent quinine and a class Ia antiarrhythmic agent.^1,2 Quinidine blocks the voltage-gated sodium (Na_v) channel Na_v1.5 in a use-dependent manner.¹ It decreases the amplitude and duration of action potentials in isolated canine ventricular myocytes.³ Quinidine inhibits K_Kr, peak I_Na, and late I_Na (IC₅₀s = 4.5, 11, and 12 μM, respectively) and can induce torsade de pointes in isolated rabbit hearts when used at a concentration of 1 μM.² It induces QT prolongation in dogs.⁴ Quinidine also binds to M₂ muscarinic acetylcholine receptors (K_i = 7.5 μM for human recombinant receptors expressed in HM2-B10 cells).⁵ Formulations containing quinidine have been used in the treatment of atrial fibrillation and ventricular arrhythmias.

Uses

A dextrorotatory stereoizomer of Quinine. Antiarrhythmic (class IA). Antimalarial.

References

1. Roden, D.M. Pharmacology and toxicology of Na_v1.5-class 1 anti-arrhythmic drugs Card. Electrophysiol. Clin. 6(4),695-704(2014).
2. Wu, L., Guo, D., Li, H., et al. Role of late sodium current in modulating the proarrhythmic and antiarrhythmic effects of quinidine Heart Rhythm 5(12),1726-1734(2008).
3. Salata, J.J., and Wasserstrom, J.A. Effects of quinidine on action potentials and ionic currents in isolated canine ventricular myocytes Circ. Res. 62(2),324-337(1988).
4. Rakhit, A., Guentert, T.W., Holford, N.H.G., et al. Pharmacokinetics and pharmacodynamics of quinidine and its metabolite, quinidine-N-oxide, in beagle dogs Eur. J. Drug Metab. Pharmacokinet. 9(4),315-324(1984).
5. Kovacs, I., Yamamura, H.I., Waite, S.L., et al. Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line J. Pharmacol. Exp. Ther. 284(2),500-507(1998).