Vogel, K. R.; Ainslie, G. R.; McConnell, A.; Roullet, J.-B.; Gibson, K. M. published the artcile< Toxicologic/transport properties of NCS-382, a γ-hydroxybutyrate (GHB) receptor ligand, in neuronal and epithelial cells: Therapeutic implications for SSADH deficiency, a GABA metabolic disorder>, Quality Control of 1223001-51-1, the main research area is NCS382 hydroxybutyrate receptor ligand toxicol transport neuron epithelium; GABA metabolism; NCS-382; Neuronal stem cells; SSADH deficiency (SSADHD); Succinic semialdehyde dehydrogenase (SSADH); γ-Hydroxybutyric acid (GHB).
We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB receptor ligand, NCS-382, using neuronal stem cells derived from mice with a targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde dehydrogenase (SSADH)-deficient mice). These animals represent a phenocopy of the human disorder of GABA metabolism, SSADH deficiency, that metabolically features accumulation of both GABA and the GABA-analog γ-hydroxybutyric acid in conjunction with a nonspecific neurol. phenotype. We demonstrate for the first time using MDCK cells that NCS-382 is actively transported and capable of inhibiting GHB transport. Following these in vitro assays with in vivo studies in aldh5a1-/- mice, we found the ratio of brain/liver GHB to be unaffected by chronic NCS-382 administration (300 mg/kg; 7 consecutive days). Employing a variety of cellular parameters (reactive oxygen and superoxide species, ATP production and decay, mitochondrial and lysosomal number, cellular viability and necrosis), we demonstrate that up to 1 mM NCS-382 shows minimal evidence of pharmacotoxicity. As well, studies at the mol. level indicate that the effects of NCS-382 at 0.5 mM are minimally toxic as evaluated using gene expression assay. The cumulative data provides increasing confidence that NCS-382 could eventually be considered in the therapeutic armament for heritable SSADH deficiency.
Toxicology In Vitro published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (aldh5a1). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem