Quinidine is a class Ia antiarrhythmic agent extracted from cinchona bark, which functions as a K⁺ channel blocker (IC₅₀=19.9µM) and inhibits cytochrome P450db activity. Quinidine reduces automaticity, slows conduction velocity, and prolongs the effective refractory period by inhibiting sodium channels on the cardiomyocyte membrane. Quinidine produces vasodilatory effects through anticholinergic action and α-receptor blockade. Quinidine can be used in research related to atrial fibrillation, atrial flutter, and supraventricular tachycardia[1-4].
In vitro, Quinidine (300µM) was used to treat C6 glioma cells for 48 hours. Quinidine significantly reduced cell proliferation, arrested the cell cycle in the G0/G1 phase, and decreased ornithine decarboxylase (ODC) activity and putrescine concentration[5]. Quinidine (90µM) was used to treat MCF-7 human breast cancer cells for 24–96 hours. Quinidine reduced the expression of the cell cycle marker Ki67 antigen and induced apoptosis and necrosis[6].
In vivo, Quinidine (2.075mg/100g; single dose) was administered intraperitoneally to Swiss mice immediately after Isoproterenol hydrochloride injection. Quinidine significantly reduced the Isoproterenol hydrochloride-induced elevation in serum glutamic-oxaloacetic transaminase (SGOT) levels and cardiac tissue lipid peroxidation, while modulating cardiac antioxidant enzyme activity and counteracting Isoproterenol hydrochloride-induced myocardial ischemic injury[7]. Quinidine (30mg/kg) was administered as a single intraperitoneal injection to NMRl male mice. Quinidine significantly increased the seizure threshold for pentylenetetrazole (PTZ)-induced tonic hind limb extension (THE)[8].
References:
[1] Grace AA, Camm AJ. Quinidine. N Engl J Med. 1998 Jan 1;338(1):35-45.
[2] Alloway JA, Salata MP. Quinidine-induced rheumatic syndromes. Semin Arthritis Rheum. 1995 Apr;24(5):315-22.
[3] Malik C, Ghosh S. Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC). Eur Biophys J. 2020 Mar;49(2):193-205.
[4] Yoshitomi S, Takahashi Y, Yamaguchi T, et al. Quinidine therapy and therapeutic drug monitoring in four patients with KCNT1 mutations. Epileptic Disord. 2019 Feb 1;21(1):48-54.
[5] Weiger TM, Colombatto S, Kainz V, et al. Potassium channel blockers quinidine and caesium halt cell proliferation in C6 glioma cells via a polyamine-dependent mechanism. Biochem Soc Trans. 2007 Apr;35(Pt 2):391-5.
[6] Wang S, Melkoumian Z, Woodfork KA, et al. Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF-7 human breast carcinoma cell line. J Cell Physiol. 1998 Sep;176(3):456-64.
[7] Chattopadhyay A, Biswas S, Bandyopadhyay D, et al. Effect of isoproterenol on lipid peroxidation and antioxidant enzymes of myocardial tissue of mice and protection by quinidine. Mol Cell Biochem. 2003 Mar;245(1-2):43-9.
[8] Jamali H, Heydari A. Effect of dextromethorphan/quinidine on pentylenetetrazole- induced clonic and tonic seizure thresholds in mice. Neurosci Lett. 2020 Jun 11;729:134988.