Bay 60-7550 is a potent inhibitor of Phosphodiesterase 2 (PDE2) purified from bovine heart with an IC50 value of 2.0±0.7nM[1]. Bay 60-7550 increased cGMP and cAMP levels and promoted cGMP signaling[2]. Bay 60-7550 has been widely used in different animal models to improve depression-like behaviors and enhance brain function[3].
In vitro, Bay 60-7550 treatment (1µM) for 24h rescued HT-22 cells from the cytotoxicity induced by 50µM corticosterone and reversed down-regulation of CBP proteins induced by corticosterone[4]. Treatment with 1µM Bay 60-7550 for 48 hours blocked oxidative stress and apoptosis in mouse primary cortical neuronal cells treated with Aβ1-42 oligomers[5].
In vivo, Bay 60-7550 treatment via intraperitoneal injection at a dose of 3mg/kg twice daily for 4 days reduced ethanol preference and intake without affecting locomotor activity in C57BL/6J mice[6]. BAY 60-7550 treatment (p.o.) at a daily dose of 1mg/kg for 21 days alleviated bilateral common carotid artery occlusion (BCCAO)-induced behavioral deficits in mice and enhanced the expression of pCREB and BDNF proteins in the hippocampus of mice[7]. Intraperitoneal injection of BAY 60-7550 at a daily dose of 3mg/kg for 14 days reversed Aβ1-42-induced memory impairment in mice[8].
References:
[1] Boess F G, Hendrix M, van der Staay F J, et al. Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance[J]. Neuropharmacology, 2004, 47(7): 1081-1092.
[2] Masood A, Huang Y, Hajjhussein H, et al. Anxiolytic effects of phosphodiesterase-2 inhibitors associated with increased cGMP signaling[J]. The Journal of pharmacology and experimental therapeutics, 2009, 331(2): 690-699.
[3] Huang X, Xiaokaiti Y, Yang J, et al. Inhibition of phosphodiesterase 2 reverses gp91phox oxidase-mediated depression-and anxiety-like behavior[J]. Neuropharmacology, 2018, 143: 176-185.
[4] Xu Y, Pan J, Chen L, et al. Phosphodiesterase-2 inhibitor reverses corticosterone-induced neurotoxicity and related behavioural changes via cGMP/PKG dependent pathway[J]. International Journal of Neuropsychopharmacology, 2013, 16(4): 835-847.
[5] Yan Y, Gao S, Avasthi S, et al. Protective effects of phosphodiesterase 2 inhibitor against Aβ1-42 induced neuronal toxicity[J]. Neuropharmacology, 2022, 213: 109128.
[6] Shi J, Liu H, Pan J, et al. Inhibition of phosphodiesterase 2 by Bay 60-7550 decreases ethanol intake and preference in mice[J]. Psychopharmacology, 2018, 235(8): 2377-2385.
[7] Soares L M, Meyer E, Milani H, et al. The phosphodiesterase type 2 inhibitor BAY 60-7550 reverses functional impairments induced by brain ischemia by decreasing hippocampal neurodegeneration and enhancing hippocampal neuronal plasticity[J]. European Journal of Neuroscience, 2017, 45(4): 510-520.
[8] Ruan L, Du K, Tao M, et al. Phosphodiesterase-2 inhibitor bay 60-7550 ameliorates Aβ-induced cognitive and memory impairment via regulation of the HPA Axis[J]. Frontiers in cellular neuroscience, 2019, 13: 432.
Bay 60-7550是一种高效磷酸二酯酶2(PDE2)抑制剂，对从牛心脏中纯化的PDE2的IC50值为2.0±0.7nM[1]。Bay 60-7550可通过提升细胞内cGMP与cAMP水平增强cGMP信号通路[2]。Bay 60-7550已广泛应用于多种动物模型中以改善抑郁样行为及增强脑功能[3]。
在体外，1µM的Bay 60-7550处理24小时能有效保护HT-22细胞免受50µM皮质酮诱导的细胞毒性，并逆转皮质酮引起的CBP蛋白下调[4]。使用1µM的Bay 60-7550处理小鼠原代皮层神经元细胞48小时，可阻断Aβ1-42寡聚体诱导的氧化应激与细胞凋亡[5]。
在体内，每日两次腹腔注射3mg/kg剂量的Bay 60-7550，连续4天，可降低C57BL/6J小鼠对乙醇的偏好和摄入量，且不影响自主活动[6]。每日口服1mg/kg剂量的Bay 60-7550，连续21天，能缓解双侧颈总动脉结扎(BCCAO)引起的小鼠行为缺陷，并增强海马组织中pCREB与BDNF蛋白表达[7]。每日腹腔注射3mg/kg剂量的Bay 60-7550，连续14天，可逆转Aβ1-42诱导的小鼠记忆功能障碍[8]。