Nebivolol hydrochloride is a third-generation, selective β1-adrenergic receptor antagonist. Nebivolol hydrochloride exerts its antihypertensive effect through a dual mechanism involving highly selective β1-blockade and activation of nitric oxide (NO)-mediated vasodilation, while having minimal impact on peripheral vascular resistance, metabolism, and sexual function[1-2]. Nebivolol hydrochloride is used in research related to hypertension, chronic heart failure, and angina pectoris[3-4].
In vitro, Nebivolol hydrochloride (0–50µM) was applied to oral squamous cell carcinoma (OSCC) cells for 24 hours. Nebivolol hydrochloride activated the endoplasmic reticulum stress signaling pathway by inducing iNOS expression, leading to G0/G1 cell cycle arrest and growth inhibition. Nebivolol hydrochloride also caused mitochondrial dysfunction, increased reactive oxygen species (ROS) levels, and induced apoptosis[5]. In melanoma cells (A2058 and B16) treated with Nebivolol hydrochloride (5–10µM) for 24 hours, Nebivolol hydrochloride reduced cAMP levels, which resulted in G0/G1 cell cycle arrest. Nebivolol hydrochloride triggered loss of mitochondrial membrane potential (ΔΨm), accumulation of ROS, activation of the mitochondrial apoptosis pathway, and suppression of migration and invasion capabilities[6].
In vivo, Nebivolol hydrochloride (15mg/kg; single dose) was administered intraperitoneally to mice with maximal electroshock-induced seizures in combination with other antiepileptic drugs. Nebivolol hydrochloride significantly attenuated the anticonvulsant effects of carbamazepine and phenobarbital[7]. Nebivolol hydrochloride (2.0μmol/kg/day) was administered via diet to apolipoprotein E (apoE) knockout mice for 4 months starting at 8 weeks of age. Nebivolol hydrochloride significantly reduced atherosclerotic plaque area in both the aortic root and the entire aorta, without affecting plasma cholesterol or triglyceride levels[8].
References:
[1] Cockcroft J. Nebivolol: a review. Expert Opin Pharmacother. 2004 Apr;5(4):893-9.
[2] de Boer RA, Voors AA, van Veldhuisen DJ. Nebivolol: third-generation beta-blockade. Expert Opin Pharmacother. 2007 Jul;8(10):1539-50.
[3] Battise D, Boland CL, Nuzum DS. Nebivolol/Valsartan: A Novel Antihypertensive Fixed-Dose Combination Tablet. Ann Pharmacother. 2019 Apr;53(4):402-412.
[4] Gao Y, Vanhoutte PM. Nebivolol: an endothelium-friendly selective β1-adrenoceptor blocker. J Cardiovasc Pharmacol. 2012 Jan;59(1):16-21.
[5] Chen Q, Jiang H, Wang Z, et al. Adrenergic Blockade by Nebivolol to Suppress Oral Squamous Cell Carcinoma Growth via Endoplasmic Reticulum Stress and Mitochondria Dysfunction. Front Pharmacol. 2021 Aug 12;12:691998.
[6] Yang S, Li Z, Yi J, et al. Nebivolol, an antihypertensive agent, has new application in inhibiting melanoma. Anticancer Drugs. 2024 Jul 1;35(6):512-524.
[7] Borowicz-Reutt KK, Banach M, Rudkowska M. Nebivolol attenuates the anticonvulsant action of carbamazepine and phenobarbital against the maximal electroshock-induced seizures in mice. Pharmacol Rep. 2020 Feb;72(1):80-86.
[8] Kus K, Gajda M, Pyka-Fosciak G, et al. The effect of nebivolol on atherogenesis in apoE-knockout mice. J Physiol Pharmacol. 2009 Dec;60(4):163-5.
Nebivolol hydrochloride是第三代β1肾上腺素受体选择性拮抗剂，Nebivolol hydrochloride通过高选择性阻断β1受体并激活一氧化氮（NO）介导的血管扩张双重机制发挥降压作用，同时对外周血管阻力、代谢及性功能影响[1-2]。Nebivolol hydrochloride可用于高血压、慢性心力衰竭和心绞痛的相关研究[3-4]。
在体外，Nebivolol hydrochloride（0-50μM）处理口腔鳞状细胞癌（OSCC）细胞24小时，Nebivolol hydrochloride通过诱导iNOS表达激活内质网应激信号通路，导致细胞周期G0/G1期阻滞和生长抑制。Nebivolol hydrochloride可引起线粒体功能障碍，增加活性氧（ROS）水平，诱导细胞凋亡[5]。Nebivolol hydrochloride（5-10μM）处理黑色素瘤细胞（A2058和B16）24小时，Nebivolol通过降低cAMP水平诱导G0/G1期细胞周期阻滞。Nebivolol hydrochloride可引起线粒体膜电位（ΔΨm）丧失和ROS积累，激活线粒体途径凋亡，并抑制迁移侵袭能力[6]。
在体内，Nebivolol hydrochloride（15mg/kg）腹腔注射处理最大电休克诱导癫痫模型小鼠（单次给药，与抗癫痫药物联用），Nebivolol hydrochloride显著减弱卡马西平和苯巴比妥的抗惊厥作用[7]。Nebivolol hydrochloride（2.0μmol/kg/day）经饲料给药处理apoE基因敲除小鼠（从8周龄开始，持续4个月），Nebivolol hydrochloride显著减轻主动脉根部和整体主动脉的动脉粥样硬化斑块面积，且不影响血浆胆固醇和甘油三酯水平[8]。