| Description | Edonerpic maleate (T-817 maleate) is a neurotrophic agent which can inhibit amyloid-β peptides (Aβ). |
| In vitro | Edonerpic maleate (T-817MA) 的处理在Aβ(1-42)存在时保护皮层神经元。经过24小时的预处理，接着持续存在Edonerpic maleate，可在0.1和1 μM时防止氧化应激引起的神经元死亡。Edonerpic maleate在0.1和1 μM几乎完全防止了GSH的减少。与对照组相比，1 μM Edonerpic maleate处理的海马切片产生了更多且更长的神经突起。Edonerpic maleate在0.1和1 μM显着增加了神经突长度。 |
| In vivo | 后设检验显示，载体及Aβ注射+高剂量Edonerpic maleate（T-817MA）组中PSA阳性细胞的平均密度显著高于Aβ注射对照组（P<0.01）。结果表明，载体及Aβ注射+高剂量Edonerpic maleate组在位置学习任务（PLT）中展现出有效的学习能力，并且这两组还展示出活跃的神经发生。使用Edonerpic maleate和donepezil治疗并不增加正常颗粒细胞的平均密度；在Aβ注射对照组、Aβ注射+高剂量Edonerpic maleate组、Aβ注射+低剂量Edonerpic maleate组以及Aβ注射+donepezil组之间，颗粒细胞的平均密度没有显著差异。 |
| Cell experiments | A cortical neuron/glia coculture is prepared. Edonerpic maleate (T-817MA) is added to the cocultures at concentrations of 0 (control), 0.01, 0.1, and 1 μM, and the cells are subsequently incubated for 5 min or 24 h. H2O2 is then added to the coculture at a concentration of 100 μM, and the cells are incubated for another 24 h. For the normal group, the preparations are maintained in the medium with neither Edonerpic maleate nor H2O2. Neuronal cell viability is quantified by measuring the Monoclonal anti-microtubule-associated protein 2 (MAP2) immunoreactivity |
| Animal experiments | Edonerpic maleate (T-817MA) (high-dose: 8.4 mg/kg and low-dose: 0.84 mg/kg) and donepezil (0.5 mg/kg) are dissolved in distilled water in a volume of 5 mL/kg.Wistar rats (7 weeks, n=47) are used in this study. All rats are given food and water ad libitum in a clear cage and handled on three consecutive days before start of the experiments. The housing area is provided a temperature-controlled environment under a 12/12 h light cycle. These rats are divided into five groups: vehicle (n=11), Aβ infusion control (n=10), Aβ infusion+high-dose Edonerpic maleate (T-817MA) (8.4 mg/kg) (n=11), Aβ infusion+low-dose Edonerpic maleate (0.84 mg/kg) (n=9) and Aβ infusion+donepezil (0.5 mg/kg) (n=7) |
| Target activity | β-Amyloid peptide: |
| Synonyms | T-817MA, T-817 maleate |
| molecular weight | 407.48 |
| Molecular formula | C20H25NO6S |
| CAS | 519187-97-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 155 mg/mL (380 mM) |
| References | 1. Hirata K,etal.A novel neurotrophic agent, T-817MA [1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate], attenuates amyloid-beta-induced neurotoxicity and promotes neurite outgrowth in rat cultured central nervous system neurons.J Pharmacol Exp Ther. 2005 Jul;314(1):252-9. 2. Kimura T,etal. T-817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused i.c.v. with amyloid-beta peptide.Br J Pharmacol. 2009 Jun;157(3):451-63. |