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Edonerpic maleate is a novel neurotrophic agent which can inhibit amyloid-β peptides (Aβ).

Edonerpic maleate (T-817MA) treatment preserves the cortical neurons in the presence of Aβ(1-42). Twenty-four hours of pretreatment, followed by the continuous presence of Edonerpic maleate, prevents oxidative stress-induced neuronal death at 0.1 and 1 μM. Edonerpic maleate almost completely prevents GSH reduction at 0.1 and 1 μM. Hippocampal slices with 1 μM Edonerpic maleate treatment generate more and much longer neurites than control slices. Edonerpic maleate significantly increases the neurite length at 0.1 and 1 μM[1].

The post hoc test indicates that the mean density of PSA-positive cells is significantly larger in the vehicle and Aβ infusion+high-dose Edonerpic maleate (T-817MA) groups than that in the Aβ infusion control group (P<0.01). The results indicate that the vehicle and Aβ infusion+high-dose Edonerpic maleate groups display efficient learning in the place learning task (PLT), while these two groups also display vigorous neurogenesis. Treatment with Edonerpic maleate and donepezil does not increase the mean density of normal granule cells; there are no significant differences in the mean granule cell density among the Aβ infusion control, Aβ infusion+high-dose Edonerpic maleate, Aβ infusion+low-dose Edonerpic maleate and Aβ infusion+donepezil groups[2].

[1]. Hirata K, et al. 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, et al. 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.

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