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.
Quinidine是一种从金鸡纳树皮中提取的Ia类抗心律失常药物，属于K+通道阻滞剂（IC50=19.9μM），可抑制细胞色素P450db（cytochrome P450db）活性。Quinidine可通过抑制心肌细胞膜上的钠离子通道来降低自律性、减慢传导速度和延长有效不应期。Quinidine通过抗胆碱作用和阻断α受体以产生血管扩张效应。Quinidine可用于心房颤动、心房扑动及室上性心动过速等相关研究[1-4]。
在体外，Quinidine（300μM）处理C6胶质瘤细胞48小时。Quinidine显著减少细胞增殖，阻滞细胞周期在G0/G1期，同时降低鸟氨酸脱羧酶（ODC）活性和腐胺浓度[5]。Quinidine（90μM）处理MCF-7人乳腺癌细胞24-96小时。Quinidine会降低细胞周期标志物Ki67抗原的表达，引发细胞凋亡与坏死[6]。
在体内，在Isoproterenol hydrochloride注射后，Quinidine（2.075mg/100g；单次）立即腹腔注射给予Swiss小鼠。Quinidine显著降低了由Isoproterenol hydrochloride素诱导的血清谷草转氨酶（SGOT）水平升高和心脏组织脂质过氧化，同时调节心脏抗氧化酶活性，并对抗Isoproterenol hydrochloride诱导的心肌缺血损伤[7]。Quinidine（30mg/kg）单次腹腔注射处理NMRI雄性小鼠。Quinidine显著增加了由戊四唑（PTZ）诱导的强直性后肢伸展（THE）的惊厥阈值[8]。