(R)-Carvedilol, the R-enantiomer of Carvedilol, is a non-selective α receptor blocker with an IC50 value of 89.20μM [1]. (R)-Carvedilol suppresses Ca2+ waves and stress-induced ventricular tachyarrhythmia without lowering heart rate or blood pressure [2]. (R)-Carvedilol has been widely used to improve the neural damage in mouse models of Alzheimer's disease (AD)[3].
In vitro, (R)-Carvedilol (5μM) treatment for 6 hours significantly inhibited doxorubicin (DOX)-induced cell death in human umbilical vein endothelial cells (HUVECs)[4].
In vivo, (R)-Carvedilol treatment via oral administration at a dose of 20mg/kg/day for 2 weeks significantly inhibited UV-induced skin carcinogenesis in SKH-1 mice, without affecting blood pressure[5]. Oral administration of (R)-Carvedilol at a dose of 3.2mg/kg/day for one month can rescue the excessive neuronal hyperactivity and memory loss in 5×FAD mice[6]. Administering 3.2mg/kg/day of (R)-Carvedilol orally for one month can rescue the memory impairment and neuronal loss in 3×TG-AD mice[7].
References:
[1] Bartsch W, Sponer G, Strein K, et al. Pharmacological characteristics of the stereoisomers of carvedilol[J]. European journal of clinical pharmacology, 1990, 38(Suppl 2): S104-S107.
[2] Zhang J, Zhou Q, Smith C D, et al. Non-β-blocking R-carvedilol enantiomer suppresses Ca2+ waves and stress-induced ventricular tachyarrhythmia without lowering heart rate or blood pressure[J]. Biochemical Journal, 2015, 470(2): 233-242.
[3] Yao J, Chen S R W. R-carvedilol, a potential new therapy for Alzheimer’s disease[J]. Frontiers in Pharmacology, 2022, 13: 1062495.
[4] Wu T, Li H, Lan Q, et al. Protective effects of S‐carvedilol on doxorubicin‐induced damages to human umbilical vein endothelial cells and rats[J]. Journal of Applied Toxicology, 2019, 39(8): 1233-1244.
[5] Sardar P K, Yeung S, Tow R, et al. Oral delivery of the non-β-blocking R-carvedilol enantiomer for skin cancer chemoprevention in SKH-1 mice[J]. AAPS open, 2025, 11(1): 1.
[6] Yao J, Sun B, Institoris A, et al. Limiting RyR2 open time prevents Alzheimer’s disease-related neuronal hyperactivity and memory loss but not β-amyloid accumulation[J]. Cell reports, 2020, 32(12).
[7] Liu Y, Yao J, Song Z, et al. Limiting RyR2 open time prevents Alzheimer's disease‐related deficits in the 3xTG‐AD mouse model[J]. Journal of Neuroscience Research, 2021, 99(11): 2906-2921.
(R)-Carvedilol是Carvedilol的R-对映体，是一种非选择性α受体阻滞剂，IC50值为89.20μM[1]。(R)-Carvedilol能够抑制钙波和应激诱导的室性快速性心律失常，且不降低心率或血压[2]。(R)-Carvedilol已被广泛用于改善阿尔茨海默病（AD）小鼠模型中的神经损伤[3]。
在体外，使用5μM的(R)-Carvedilol处理人脐静脉内皮细胞（HUVECs）6小时，显著抑制了阿霉素（DOX）诱导的细胞死亡[4]。
在体内，每日口服20mg/kg剂量的(R)-Carvedilol，连续2周，显著抑制了SKH-1小鼠中紫外线诱导的皮肤癌发生，且不影响血压[5]。每日口服3.2mg/kg剂量的(R)-Carvedilol，持续一个月，可以挽救5×FAD小鼠中过度的神经元过度活跃和记忆丧失[6]。每日口服3.2mg/kg剂量的(R)-Carvedilol一个月，可以挽救3×TG-AD小鼠的记忆障碍和神经元损失[7]。