Propranolol is a non-selective β-adrenergic receptor (βAR) antagonist, exhibiting high affinity for both β1AR and β2AR, with Ki values of 1.8 nM and 0.8 nM, respectively[1]. It inhibits the binding of [3H]-DHA to rat brain membrane preparations with an IC50 of 12 nM[2]. Propranolol is used in research related to hypertension, pheochromocytoma, myocardial infarction, arrhythmias, angina, and hypertrophic cardiomyopathy[3].
In vitro, propranolol increases total ERK1/2 levels in a dose-dependent manner within the concentration range of 10-7 M to 10-3 M, after 24 and 48 hours of treatment, and specifically activates ERK1/2 at a concentration of 10-5 M[4]. After 24 hours of treatment at a concentration of 10-4 M, and after 48 hours at 10-9 M, propranolol significantly reduces the proliferation of HemSC cells[4]. Moreover, propranolol treatment at concentrations ranging from 50µM to 200µM for 24 hours increases the number of Annexin V-positive HemSCs, activates caspase-3, thereby rapidly inducing apoptosis in HemSC cells[4].
In vivo, propranolol (40 mg/kg/d, p.o.) significantly reduces the diameter and blood flow of vessels in an infantile hemangioma (IH) mouse model, while also promoting the activation of ERK1/2 within IH cells[4]. In the Tg2576 Alzheimer's disease transgenic mouse model, propranolol (5mg/kg/d, i.p.) is able to improve cognitive deficits demonstrated in novel object recognition and fear conditioning tests, reduce the increase in Aβ42 levels in the hippocampus, increase in Akt phosphorylation, and excessive phosphorylation of Tau[5].
References:
[1] Galandrin S, et al. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol. 2006 Nov;70(5):1575-84.
[2] Briley M, et al. Evidence against beta-adrenoceptor blocking activity of diltiazem, a drug with calcium antagonist properties. Br J Pharmacol. 1980 Aug;69(4):669-73.
[3] Al-Majed AA, et al. Propranolol. Profiles Drug Subst Excip Relat Methodol. 2017;42:287-338.
[4] Munabi NC, et al. Propranolol Targets Hemangioma Stem Cells via cAMP and Mitogen-Activated Protein Kinase Regulation. Stem Cells Transl Med. 2016 Jan;5(1):45-55.
[5] Marta D , Gorka G ,RamÍrez MarÍa J. Propranolol reduces cognitive deficits, amyloid and tau pathology in Alzheimer's transgenic mice[J]. Int J Neuropsychopharmacol, 2013(10): 2245-2257.
普萘洛尔(Propranolol)是一种非选择性的 β-adrenergic receptor (βAR) 拮抗剂,对 β1AR 和 β2AR 具有高亲和力,Ki值分别为 1.8 nM和0.8 nM[1]。 Propranolol 抑制[3H]-DHA与大鼠脑膜制剂的结合,IC50为12 nM[2]。Propranolol 用于高血压,嗜铬细胞瘤,心肌梗塞,心律不齐,心绞痛和肥大心肌病的相关研究[3]。
在体外,Propranolol通过剂量依赖的方式在10-7M到10-3M浓度范围内,经过24小时和48小时的处理,可以增加总ERK1/2水平,并且在10-5M的浓度下特异性激活ERK1/2[4]。Propranolol在处理浓度为10-4M持续24小时后,以及10-9M处理48小时后,能显著降低HemSCs细胞的增殖[4]。此外,在50µM到200µM浓度范围内,Propranolol处理24小时能够增加Annexin V阳性的HemSC数量,激活caspase-3,从而快速诱导HemSC细胞的凋亡[4]。
在体内,Propranolol(40 mg/kg/d,p.o.)在婴儿血管瘤(IH)小鼠模型中,显著减少了血管的直径和血流量,同时促进了IH细胞内ERK 1/2的活化[4]。在Tg2576阿尔茨海默病转基因小鼠模型中,Propranolol(5mg/kg/d,i.p.)能够改善在新物体识别和恐惧调节测试中表现出的认知障碍,减少海马体中Aβ42水平的增加,Akt 磷酸化的增加和Tau 过度磷酸化[5]。