NNC 05-2090 hydrochloride is a GABA uptake inhibitor selective for the BGT-1 (mGAT-2) transporter[1]. NNC 05-2090 hydrochloride can be used for research related to epilepsy and neurological diseases[2-3].
In vitro, NNC 05-2090 hydrochloride (1.25–20μM) treated primary hepatocytes for 15 minutes, followed by stimulation with TNF-α (20ng/ml)/ActD (200ng/ml) for 24 hours. NNC 05-2090 hydrochloride inhibited TNF-α-mediated hepatocyte apoptosis and upregulated the expression of the anti-apoptotic gene c-Met[4]. NNC 05-2090 hydrochloride (50–150μM) treated rat astrocytes and HepG2 cells for 1 hour. NNC 05-2090 hydrochloride inhibited betaine transport through BGT1 and reversed the osmoprotective effect of betaine against cell shrinkage under hypertonic conditions[5].
In vivo, NNC 05-2090 hydrochloride (8mg/kg) was administered intraperitoneally to mice 1 hour after intracerebroventricular injection of Aβ25-35. NNC 05-2090 hydrochloride significantly attenuated the preventive effect of betaine on Aβ25-35-induced cognitive impairment but did not affect betaine's inhibition of brain oxidative stress[6]. NNC 05-2090 hydrochloride (0–242μmol/kg) was administered intraperitoneally to DBA/2 mice 1 hour before acoustic stimulation. NNC 05-2090 hydrochloride dose-dependently antagonized sound-induced tonic and clonic convulsions[7].
References:
[1] Jinzenji A, Sogawa C, Miyawaki T, et al. Antiallodynic action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a betaine/GABA transporter inhibitor. J Pharmacol Sci. 2014;125(2):217-26.
[2] Thomsen C, Sørensen PO, Egebjerg J. 1-(3-(9H-carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidinol, a novel subtype selective inhibitor of the mouse type II GABA-transporter. Br J Pharmacol. 1997 Mar;120(6):983-5.
[3] Kunisawa K, Kido K, Nakashima N, et al. Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus. Eur J Pharmacol. 2017 Feb 5;796:122-130.
[4] Liu Z, Li Q, Shen R, Ci L, et al. Betaine/GABA transporter-1 (BGT-1) deficiency in mouse prevents acute liver failure in vivo and hepatocytes apoptosis in vitro. Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165634.
[5] Pukale DD, Farrag M, Gudneppanavar R, et al. Osmoregulatory Role of Betaine and Betaine/γ-Aminobutyric Acid Transporter 1 in Post-Traumatic Syringomyelia. ACS Chem Neurosci. 2021 Oct 6;12(19):3567-3578.
[6] Ibi D, Tsuchihashi A, Nomura T, et al. Involvement of GAT2/BGT-1 in the preventive effects of betaine on cognitive impairment and brain oxidative stress in amyloid β peptide-injected mice. Eur J Pharmacol. 2019 Jan 5;842:57-63.
[7] Dalby NO, Thomsen C, Fink-Jensen A, et al. Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05-2090, not acting preferentially on GAT-1. Epilepsy Res. 1997 Jul;28(1):51-61.
NNC 05-2090 hydrochloride是一种GABA摄取抑制剂，对BGT-1（mGAT-2）转运体具有选择性[1]。NNC 05-2090 hydrochloride可用于癫痫和神经系统疾病的相关研究[2-3]。
在体外，NNC 05-2090 hydrochloride（1.25–20μM））处理原代肝细胞15分钟，随后以TNF-α（20ng/ml）/ActD（200ng/ml）刺激24小时。NNC 05-2090 hydrochloride可抑制TNF-α介导的肝细胞凋亡，并上调抗凋亡基因c-Met的表达[4]。NNC 05-2090 hydrochloride（50–150μM）处理大鼠星形胶质细胞及HepG2细胞1小时。NNC 05-2090 hydrochloride可抑制甜菜碱通过BGT1的转运，同时逆转甜菜碱在高渗条件下对细胞皱缩的保护作用[5]。
在体内，NNC 05-2090 hydrochloride（8mg/kg）在Aβ25-35侧脑室注射后1小时腹腔注射处理小鼠。NNC 05-2090 hydrochloride显著减弱了甜菜碱对Aβ25-35诱导的认知障碍的预防作用，但不影响甜菜碱对大脑氧化应激的抑制作用[6]。NNC 05-2090 hydrochloride（0–242μmol/kg）在声刺激前1小时腹腔注射于DBA/2小鼠。NNC 05-2090 hydrochloride以剂量依赖性地拮抗了声音诱发的强直性和阵挛性惊厥[7]。