Memantine hydrochloride is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, with the IC50 values of 0.5-1μM[1]. Memantine hydrochloride protects neurons against toxicity caused by overactivation of NMDAR and blocks the effects of tonic pathologically elevated levels of glutamate that may lead to neuronal dysfunction[2]. Memantine hydrochloride has been used in animal models to treat various types of dementia and neurodegenerative diseases[3].
In vitro, Memantine hydrochloride treatment at 50μM for 24 hours significantly alleviated the decrease in rat hippocampal cell viability induced by amyloid protein β1-42, increased the number of living cells, and enhanced cell viability[4]. Treatment with 10μM Memantine hydrochloride for 6 hours attenuated the oxidative stress induced by oxygen-glucose deprivation/reperfusion in human umbilical vein endothelial cells (HUVECs), increased the expression of Nrf2 and HO-1, and enhanced cell viability[5]. Treatment with 250μM Memantine hydrochloride for 48 hours resulted in a significant increase in the expression level of the pro-apoptotic protein Bax in LNCaP cells, and induced cell cycle arrest at the G0/G1 phase[6].
In vivo, Memantine hydrochloride treatment (20mg/kg) by gavage daily for 2 months can improve the spatial learning ability of APP/PS1 mice and alleviate memory impairment[7]. Continuous intraperitoneal injection of 10mg/kg/day dose of Memantine hydrochloride for 10 consecutive days could alleviate the parasitemia in BALB/c mice infected with Trypanosoma cruzi, resulting in a reduction in cardiac parasitic load and inflammatory infiltration, and an increase in the survival rate of the mice[8].
References:
[1] Kotermanski S E, Johnson J W. Mg2+ imparts NMDA receptor subtype selectivity to the Alzheimer's drug memantine[J]. Journal of Neuroscience, 2009, 29(9): 2774-2779.
[2] Witt A, Macdonald N, Kirkpatrick P. Memantine hydrochloride[J]. Nature reviews Drug discovery, 2004, 3(2): 109-110.
[3] Peng D, Yuan X, Zhu R. Memantine hydrochloride in the treatment of dementia subtypes[J]. Journal of Clinical Neuroscience, 2013, 20(11): 1482-1485.
[4] Rozumna N M, Hanzha V V, Lukyanetz E A. Memantine protects the cultured rat hippocampal neurons treated by NMDA and amyloid β1–42[J]. Frontiers in Neuroscience, 2023, 17: 1269664.
[5] Lv X, Li Q, Mao S, et al. The protective effects of memantine against inflammation and impairment of endothelial tube formation induced by oxygen-glucose deprivation/reperfusion[J]. Aging (Albany NY), 2020, 12(21): 21469.
[6] Albayrak G, Konac E, Dikmen A U, et al. Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells[J]. Human & experimental toxicology, 2018, 37(9): 953-958.
[7] Li P, Xu J, Gu H, et al. Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection[J]. BMC neuroscience, 2021, 22(1): 41.
[8] Santos Souza H F, Rocha S C, Damasceno F S, et al. The effect of memantine, an antagonist of the NMDA glutamate receptor, in in vitro and in vivo infections by Trypanosoma cruzi[J]. PLoS neglected tropical diseases, 2019, 13(9): e0007226.
Memantine hydrochloride是一种非竞争性N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂，IC50值为0.5-1μM[1]。Memantine hydrochloride通过保护神经元免受NMDAR过度激活引起的毒性作用，并阻断病理性升高的谷氨酸水平导致的神经元功能障碍[2]。Memantine hydrochloride已广泛应用于多种痴呆和神经退行性疾病动物模型的治疗研究[3]。
在体外，50μM 的Memantine hydrochloride处理24小时可显著缓解β淀粉样蛋白（Aβ1-42）诱导的大鼠海马细胞活力下降，增加活细胞数量并增强细胞活性[4]。10μM的Memantine hydrochloride处理人脐静脉内皮细胞（HUVECs）6小时能缓解氧糖剥夺/再灌注诱导的氧化应激，增加Nrf2和HO-1表达并提高细胞活力[5]。250μM的Memantine hydrochloride处理LNCaP细胞48小时可显著上调促凋亡蛋白Bax表达水平，并诱导细胞周期阻滞于G0/G1期[6]。
在体内，APP/PS1小鼠每日灌胃Memantine hydrochloride（20mg/kg；持续2个月）可改善空间学习能力并缓解记忆损伤[7]。克氏锥虫感染的BALB/c小鼠连续10天每日腹腔注射10mg/kg剂量的Memantine hydrochloride能减轻寄生虫血症，降低心脏寄生虫负荷和炎症浸润，并提高生存率[8]。