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].
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