Nadolol is a non-selective and orally active beta-adrenergic antagonist with antihypertensive and antiarrhythmic activities [1]. Nadolol can inhibit the calmodulin-activated Ca2+-ATPase of human erythrocyte membranes [2]. Nadolol has been widely used to reduce heart rate at rest and during exercise and to reduce plasma renin activity[3].
In vitro, Nadolol treatment (10µM) for 24 hours significantly increased Gαs protein levels and enhanced basal cAMP levels in β2AR-expressing HEK 293 cells[4]. Treatment with 250µM Nadolol for 48h induced apoptosis and decreased mitochondrial membrane potential in A549 cells[5].
In vivo, Nadolol treatment via intraperitoneal injection at a single dose of 20mg/kg significantly reduced the number and area of lung metastases in a B16F10 cell-xenograft mouse model under acute social stress during 15 days[6]. A single dose of 5mg/kg Nadolol was injected intraperitoneally at 1h after reperfusion, which significantly reversed the increases in neurological deficit score and infarct volume in the ischemic stroke rats[7].
References:
[1] Kalsoom S, Zamir A, Rehman A U, et al. Clinical pharmacokinetics of nadolol: A systematic review[J]. Journal of Clinical Pharmacy and Therapeutics, 2022, 47(10): 1506-1516.
[2] Meltzer H L, Kassir S. Inhibition of calmodulin-activated Ca2+-ATPase by propranolol and nadolol[J]. Biochimica et Biophysica Acta (BBA)-General Subjects, 1983, 755(3): 452-456.
[3] Heel R C, Brogden R N, Pakes G E, et al. Nadolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris[J]. Drugs, 1980, 20(1): 1-23.
[4] Peng H, Bond R A, Knoll B J. The effects of acute and chronic nadolol treatment on β2AR signaling in HEK293 cells[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2011, 383(2): 209-216.
[5] Kavakcıoğlu Yardımcı B, Geyikoglu F, Aysin F, et al. The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines[J]. Molecular Biology Reports, 2021, 48(5): 4009-4019.
[6] Vegas O, Garmendia L, Arregi A, et al. Effects of antalarmin and nadolol on the relationship between social stress and pulmonary metastasis development in male OF1 mice[J]. Behavioural brain research, 2009, 205(1): 200-206.
[7] Yang X Y, Zhu W J, Chen D, et al. Nadolol Attenuates Brain Cell Ferroptosis in Ischemic Stroke Rats by Targeting the HOIL-1/IRP2 Pathway[J]. CNS & Neurological Disorders-Drug Targets, 2025, 24(5): 397-408.
Nadolol是一种非选择性、口服有效的β-肾上腺素能拮抗剂，具有抗高血压和抗心律失常活性[1]。Nadolol可抑制人红细胞膜钙调蛋白激活的Ca2+-ATP酶[2]。Nadolol已被广泛用于降低静息和运动时的心率，并降低血浆肾素活性[3]。
在体外，使用10µM的Nadolol处理表达β2AR的HEK 293细胞24小时，显著增加了Gαs蛋白水平并增强了基础cAMP水平[4]。使用250µM的Nadolol处理48小时，诱导了A549细胞凋亡并降低了线粒体膜电位 [5]。
在体内，在急性社会应激期间，单次腹腔注射20mg/kg的Nadolol，显著减少了B16F10细胞异种移植小鼠模型中的肺转移灶数量和面积（持续15天）[6]。再灌注后1小时单次腹腔注射5mg/kg的Nadolol，显著逆转了缺血性卒中大鼠的神经功能缺损评分和梗死体积的增加[7]。