ICI 118,551 hydrochloride is a selective β2-adrenergic receptor antagonist [1]. By competitively blocking β2-adrenergic receptors, ICI 118,551 hydrochloride inhibits epinephrine- or norepinephrine-mediated signal transduction, thereby affecting β2-receptor-related physiological processes in the cardiovascular and respiratory systems [2-3]. ICI 118,551 hydrochloride is commonly used to treat heart failure [4].
In HeLa 9xHRE-Luc cell, ICI 118,551 hydrochloride (0–200μM; 24h) decreases viability in hemangioblastomas by inducing cell apoptosis [5]. In induced pluripotent stem cells, ICI 118,551 hydrochloride (0.3μM; 30min) pretreatment of cells significantly inhibited the increase in KDR expression induced by L-isoproterenol [6]. In BxPC-3 and MIA PaCa-2 cells, ICI 118,551 hydrochloride (1-100μM; 24h) enhanced the antiproliferative and proapoptotic effects induced by gemcitabine [7].
In 3xTg-alzheimer's disease (AD) mice, ICI 118,551 hydrochloride (1 mg/kg; ip; 45 days) exacerbates cognitive deficits in the AD mouse model [8]. In wild-type mice, ICI 118,551 hydrochloride (0.7mg/kg; iv; 14d) increases PKA activity [9].
References:
[1]. Billman G E, Castillo L C, Hensley J, et al. β2-Adrenergic receptor antagonists protect against ventricular fibrillation: in vivo and in vitro evidence for enhanced sensitivity to β2-adrenergic stimulation in animals susceptible to sudden death[J]. Circulation, 1997, 96(6): 1914-1922.
[2]. Denda M, Fuziwara S, Inoue K. β2-adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption[J]. Journal of Investigative Dermatology, 2003, 121(1): 142-148.
[3]. Boshchenko A A, Kurbatov B K, Kilin M, et al. Role of β-Adrenergic Receptors in Stress-Induced Cardiac Injury[J]. Bulletin of Experimental Biology and Medicine, 2025: 1-4.
[4]. Gong H, Sun H, Koch W J, et al. Specific β2AR blocker ICI 118,551 actively decreases contraction through a Gi-coupled form of the β2AR in myocytes from failing human heart[J]. Circulation, 2002, 105(21): 2497-2503.
[5]. Cuesta A M, Albiñana V, Gallardo-Vara E, et al. The β2-adrenergic receptor antagonist ICI-118,551 blocks the constitutively activated HIF signalling in hemangioblastomas from von Hippel-Lindau disease[J]. Scientific reports, 2019, 9(1): 10062.
[6]. Ishizuka T, Goshima H, Ozawa A, et al. Involvement of β-adrenoceptors in the differentiation of human induced pluripotent stem cells into mesodermal progenitor cells[J]. European Journal of Pharmacology, 2014, 740: 28-34.
[7]. Shan T, Ma Q, Zhang D, et al. β2-adrenoceptor blocker synergizes with gemcitabine to inhibit the proliferation of pancreatic cancer cells via apoptosis induction[J]. European journal of pharmacology, 2011, 665(1-3): 1-7.
[8]. Branca C, Wisely E V, Hartman L K, et al. Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease[J]. Neurobiology of aging, 2014, 35(12): 2726-2735.
[9]. Liu X, Callaerts-Vegh Z, Evans K L J, et al. Chronic infusion of β-adrenoceptor antagonist and inverse agonists decreases elevated protein kinase A activity in transgenic mice with cardiac-specific overexpression of human β2-adrenoceptor[J]. Journal of cardiovascular pharmacology, 2002, 40(3): 448-455.
ICI 118,551 hydrochloride是一种选择性β2-肾上腺素受体拮抗剂 [1]。通过竞争性阻断β2-肾上腺素受体，ICI 118,551 hydrochloride抑制肾上腺素或去甲肾上腺素介导的信号转导，从而影响心血管和呼吸系统中与β2受体相关的生理过程 [2-3]。ICI 118,551 hydrochloride常用于治疗心力衰竭 [4]。
在HeLa 9xHRE-Luc细胞中，ICI 118,551 hydrochloride（0-200μM；24 h）通过诱导细胞凋亡降低血管母细胞瘤的存活率 [5]。在诱导性多能干细胞中，ICI 118,551 hydrochloride（0.3μM；30min）预处理细胞可显著抑制L-异丙肾上腺素诱导的KDR表达增加 [6]。在BxPC-3和MIA PaCa-2细胞中，ICI 118,551 hydrochloride（1-100μM；24h）可增强吉西他滨诱导的抗增殖和促凋亡作用 [7]。
在3xTg-阿尔茨海默症（AD）小鼠中，ICI 118,551 hydrochloride（1mg/kg；ip；45d）会加剧AD小鼠模型的认知缺陷 [8]。在野生型小鼠中，ICI 118,551 hydrochloride（0.7mg/kg；iv；14d）可提高PKA活性 [9]。