ZD 7288 is a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker [1]. ZD 7288 reduces cellular spontaneous activity and excitability by reducing If/Ih currents [2]. ZD 7288 is commonly used in areas such as arrhythmias, neuropathic pain, or irritable bowel syndrome (IBS) [3-4].
In mouse embryonic stem cells, ZD 7288 (0.1-30μM; 72h) decreased the proportion of cells in G0/G1 phase and increase the proportion of cells in S phase [5]. In HEK293 cells, ZD 7288 (0.1-100μM; 2h) inhibits Na+ currents in cells transfected with Nav 1.4 plasmid [6]. In α-TC6 cells, blocking HCN channels with ZD 7288 (100μM; 30min) significantly increases the intracellular calcium concentration [7].
In shrews, ZD 7288 (0-1mg/kg; ip; single injection) induces vomiting in a dose-dependent manner [8]. In C57BL/6 mice, ZD 7288 (6.25μg/kg, 12.5μg/kg; ip; single injection) inhibits sevoflurane-induced agitation [9].
References:
[1]. Zhang X, Min X, Xu X, et al. ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity[J]. Neural Regeneration Research, 2016, 11(5): 779-786.
[2]. Gasparini S, DiFrancesco D. Action of the hyperpolarization-activated current (I h) blocker ZD 7288 in hippocampal CA1 neurons[J]. Pflügers Archiv, 1997, 435(1): 99-106.
[3]. Chen Y, Lin C, Tang Y, et al. ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats[J]. World journal of gastroenterology: WJG, 2014, 20(8): 2091.
[4]. Yang L, Liu X, Yao K, et al. HCN channel antagonist ZD7288 ameliorates neuropathic pain and associated depression[J]. Brain Research, 2019, 1717: 204-213.
[5]. Lau Y T, Wong C K, Luo J, et al. Effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers on the proliferation and cell cycle progression of embryonic stem cells[J]. Pflügers Archiv-European Journal of Physiology, 2011, 461(1): 191-202.
[6]. Wu X, Liao L, Liu X, et al. Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?[J]. Channels, 2012, 6(6): 438-442.
[7]. Zhang Y, Zhang N, Gyulkhandanyan A V, et al. Presence of functional hyperpolarisation-activated cyclic nucleotide-gated channels in clonal alpha cell lines and rat islet alpha cells[J]. Diabetologia, 2008, 51(12): 2290-2298.
[8]. Zhong W, Darmani N A. The Hcn Channel blocker Zd7288 induces Emesis in the least shrew (Cryptotis parva)[J]. Frontiers in Pharmacology, 2021, 12: 647021.
[9]. Liang P, Xu-Bin H, Feng-Shan L, et al. Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blocker ZD7288 Prevents Sevoflurane-Induced Hyperactivity in A Novel Mice Behavioral Model[J]. Journal of Anesthesia and Perioperative Medicine (JAPM), 2017, 4(5): 205.
ZD 7288是一种超极化激活环核苷酸门控（HCN）通道阻滞剂 [1]。ZD 7288通过降低If/Ih电流来降低细胞自发活动和兴奋性 [2]。ZD 7288常用于治疗心律失常、神经性疼痛或肠易激综合征（IBS） [3-4]。
在小鼠胚胎干细胞中，ZD 7288（0.1-30μM；72h）降低G0/G1期细胞的比例，并增加了S期细胞的比例 [5]。在HEK293细胞中，ZD 7288（0.1-100μM；2h）抑制了转染Nav 1.4质粒的细胞中的Na+电流 [6]。在α-TC6细胞中，用ZD 7288（100μM；30min）阻断HCN通道可显著升高细胞内钙离子浓度 [7]。
在鼩鼱中，ZD 7288（0-1mg/kg；ip；单次注射）以剂量依赖性方式诱发呕吐 [8]。在C57BL/6小鼠中，ZD 7288（6.25μg/kg，12.5μg/kg；ip；单次注射）可抑制七氟醚引起的躁动 [9]。