Dexpramipexole (Dihydrochloride), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. Dexpramipexole appears promising as a GC-sparing (glucocorticoid) agent without apparent toxicity in a subset of subjects with GC-responsive HESs (Hypereosinophilic syndromes)[3]. Dexpramipexole increased mitochondrial ATP production in cultured neurons or glia and reduces energy failure, prevents intracellular Ca2+ overload and affords cytoprotection when cultures are exposed to OGD (oxygen-glucose deprivation). Post-ischaemic treatment with dexpramipexole, at doses consistent with those already used in ALS (amyotrophic lateral sclerosis) patients, reduced brain infarct size and ameliorated neuroscore in mice subjected to transient or permanent MCAo (middle cerebral artery occlusion)[4]. Moreover, patch-clamp recordings in rat hippocampal neurons revealed that Dexpramipexole dose-dependently inhibited (IC50 of 814 nM) the IA current, a rapidly-inactivating K+ current that negatively regulates neuronal excitability as well as cognition and memory processes. Dexpramipexole counteracted both scopolamine-induced spatial memory loss in rats challenged in Morris Water Maze test and memory retention in rats undergoing Novel Object Recognition[5]. Dexpramipexole treatment produced profound eosinophil-lowering in peripheral blood and nasal polyp tissue[6].
Dexpramipexole 2HCl/右旋普拉克索二盐酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
organotypic hippocampal slices
10 µM
30 min OGD
prevented ATP depletion and neuronal death
Br J Pharmacol. 2018 Jan;175(2):272-283.
cortical neurons
10 µM
6 h
increased ATP content
Br J Pharmacol. 2018 Jan;175(2):272-283.
hippocampal neurons
10 µM
10 min before OGD
reduced intracellular Ca2+ increase and DCD
Br J Pharmacol. 2018 Jan;175(2):272-283.
mixed cortical cell cultures
10 µM
2 h OGD
reduced ATP loss and improved energy recovery
Br J Pharmacol. 2018 Jan;175(2):272-283.
glial cells
10 µM
6 h
increased ATP content
Br J Pharmacol. 2018 Jan;175(2):272-283.
Mouse organotypic cortical cultures
3-10 μM
48 h
To evaluate the neuroprotective effect of Dexpramipexole against energy depletion-induced toxicity, results showed significant reduction in cell death.
Br J Pharmacol. 2020 Jul;177(14):3342-3356.
Mouse optic nerve
3-10 μM
24 h
To evaluate the effect of Dexpramipexole on ATP content in optic nerves, results showed a dose-dependent counteraction of ATP drop.
Br J Pharmacol. 2020 Jul;177(14):3342-3356.
Mouse dorsal root ganglia (DRG)
3-10 μM
24 h
To evaluate the effect of Dexpramipexole on ATP content in DRG, results showed a dose-dependent increase in ATP levels.
Br J Pharmacol. 2020 Jul;177(14):3342-3356.
mouse organotypic cortical cultures
3-10 μM
48 h
To evaluate the neuroprotective effect of Dexpramipexole, it was found to significantly reduce cytotoxicity induced by oligomycin or veratridine
Br J Pharmacol. 2020 Jul;177(14):3342-3356.
rat dorsal root ganglia (DRG)
3-10 μM
24 h
To evaluate the effect of Dexpramipexole on ATP content, it was found to increase ATP content in a dose-dependent manner
Br J Pharmacol. 2020 Jul;177(14):3342-3356.
mouse optic nerve
3-10 μM
24 h
To evaluate the effect of Dexpramipexole on ATP content, it was found to counteract ATP drop in a concentration-dependent manner
Br J Pharmacol. 2020 Jul;177(14):3342-3356.
hippocampal neurons
10 µM
reduced intracellular Ca2+ increase and DCD
Br J Pharmacol. 2018 Jan;175(2):272-283.
mixed cortical cells
10 µM
2 h OGD
reduced ATP loss and improved energy recovery
Br J Pharmacol. 2018 Jan;175(2):272-283.
glial cells
10 µM
6 h
increased ATP content
Br J Pharmacol. 2018 Jan;175(2):272-283.
cortical neurons
10 µM
6 h
increased ATP content
Br J Pharmacol. 2018 Jan;175(2):272-283.
Dexpramipexole 2HCl/右旋普拉克索二盐酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Transient or permanent middle cerebral artery occlusion (MCAo)
Intraperitoneal injection
3 mg/kg
Twice daily for 7 days
Reduced brain infarct size and improved neuroscore
Br J Pharmacol. 2018 Jan;175(2):272-283.
Mice
Transient or permanent middle cerebral artery occlusion
Intraperitoneal injection
3 mg/kg
Twice daily for 7 days
Reduced brain infarct size and improved neuroscore
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