NNC 711是一种GABA转运体1（GAT-1）抑制剂，可抑制GAT-1（IC50=0.04nM）、rGAT-1（IC50=0.38nM）、rGAT-2（IC50=171nM）、hGAT-3（IC50=1700nM）、rGAT-3（IC50=349nM）、hBGT-3（IC50=622nM）。
Cas No.:145645-62-1
Sample solution is provided at 25 µL, 10mM.
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NNC 711 is a GABA transporter 1 (GAT-1) inhibitor that inhibits GAT-1 (IC₅₀=0.04nM), rGAT-1 (IC₅₀=0.38nM), rGAT-2 (IC₅₀=171nM), hGAT-3 (IC₅₀=1700nM), rGAT-3 (IC₅₀=349nM), and hBGT-3 (IC₅₀=622nM)[1-2]. NNC 711 enhances GABAergic neurotransmission by inhibiting GABA reuptake and is used in research related to anticonvulsant, analgesic, and cognitive enhancement effects[3-4].
In vitro, LM(tk-) cells and COS cells stably expressing human/rat GAT-1, rat GAT-2, human/rat GAT-3, and human BGT-1 were treated with NNC 711 (0.04–0.38μM) for 10 minutes. NNC 711 potently and selectively inhibited the uptake of gamma-aminobutyric acid (GABA)[5]. NNC 711 (50–100μM) was added 5 minutes prior to the GABA uptake assay. NNC 711 significantly inhibited GABA uptake in mixed neuronal-glial cultures but did not block GABA uptake in purified avian Müller glial cells[6].
In vivo, normal and unilaterally 6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats were subjected to continuous perfusion of NNC 711 (30μM) via retrodialysis. In the presence of noisy vestibular stimulation (SVS), NNC 711 significantly enhanced and sustained the release of gamma-aminobutyric acid (GABA) in the substantia nigra[7]. Neuropathic allodynic Sprague-Dawley male rats were administered a single intrathecal injection of NNC 711 (20μg per rat). At 30 minutes post-administration, NNC 711 significantly attenuated nerve injury-induced mechanical allodynia[8].
References:
[1] Bernásková K, Slamberová R, Mares P. GABA uptake blocker NNC-711 exhibits marked anticonvulsant action in two cortical epileptic models in immature rats. Epilepsia. 1999 Sep;40(9):1184-9.
[2] O'Connell AW, Fox GB, Kjøller C, et al. Anti-ischemic and cognition-enhancing properties of NNC-711, a gamma-aminobutyric acid reuptake inhibitor. Eur J Pharmacol. 2001 Jul 13;424(1):37-44.
[3] Kubová H, Haugvicová R, Mares P. Effects of NNC 711, a GABA uptake inhibitor, on pentylenetetrazol-induced seizures in developing and adult rats. Naunyn Schmiedebergs Arch Pharmacol. 1998 Sep;358(3):334-41.
[4] Suzdak PD, Frederiksen K, Andersen KE, et al. NNC-711, a novel potent and selective gamma-aminobutyric acid uptake inhibitor: pharmacological characterization. Eur J Pharmacol. 1992 Dec 2;224(2-3):189-98.
[5] Borden LA, Murali Dhar TG, Smith KE, et al. Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol. 1994 Oct 14;269(2):219-24.
[6] De Sampaio Schitine C, Kubrusly RC, De Melo Reis RA, et al. GABA uptake by purified avian Müller glia cells in culture. Neurotox Res. 2007 Sep;12(2):145-53.
[7] Samoudi G, Nissbrandt H, Dutia MB, et al. Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats. PLoS One. 2012;7(1):e29308.
[8] Lee J, Back SK, Lim EJ, et al. Are spinal GABAergic elements related to the manifestation of neuropathic pain in rat? Korean J Physiol Pharmacol. 2010 Apr;14(2):59-69.
NNC 711是一种GABA转运体1（GAT-1）抑制剂，可抑制GAT-1（IC50=0.04nM）、rGAT-1（IC50=0.38nM）、rGAT-2（IC50=171nM）、hGAT-3（IC50=1700nM）、rGAT-3（IC50=349nM）、hBGT-3（IC50=622nM）[1-2]。NNC 711通过抑制GABA再摄取来增强GABA能神经传递，NNC 711可用于抗惊厥、镇痛和认知增强的相关研究[3-4]。
在体外，NNC 711（0.04–0.38μM）处理稳定表达人/大鼠GAT-1、大鼠GAT-2、人/大鼠GAT-3及人BGT-1的LM（tk-）细胞和COS细胞10分钟。NNC 711可高选择性地抑制γ-氨基丁酸（GABA）的摄取[5]。NNC 711（50–100μM）在GABA摄取实验前5分钟加入。NNC 711显著抑制混合神经元-胶质细胞培养物中的GABA摄取，但对纯化的禽类Müller胶质细胞的GABA摄取无阻断作用[6]。
在体内，NNC 711（30μM）通过反向透析持续灌注，处理正常及6-羟基多巴胺（6-OHDA）单侧损伤的Sprague-Dawley大鼠。在存在噪音前庭刺激（SVS）的条件下，NNC 711可显著增强并维持黑质（substantia nigra）中γ-氨基丁酸（GABA）的释放[7]。NNC 711（20μg/只大鼠）通过单次鞘内注射处理神经病理性痛觉超敏（allodynic）Sprague-Dawley雄性大鼠。在给药后30分钟，NNC 711可显著减轻神经损伤引起的机械性痛觉超敏[8]。
| Cell experiment [1]: | |
Cell lines | LM(tk-) cells (mouse fibroblast cell line) stably transfected to express human GAT-1, rat GAT-2, human GAT-3, or human BGT-1; and COS cells (African green monkey kidney cell line) transiently transfected to express rat GAT-1 or rat GAT-3 |
Preparation Method | Stable transfectants were grown in DMEM. For the transport assay, cells grown in 24-well plates were washed with Hepes-buffered saline (HBS) and equilibrated at 37°C. Cells were treated with NNC 711 (0.04–0.38μM). |
Reaction Conditions | 0.04–0.38μM; 10min. |
Applications | NNC 711 potently and selectively inhibited GABA uptake mediated by the GABA transporter GAT-1 (IC₅₀ of 0.04μM for human GAT-1 and 0.38μM for rat GAT-1), while showing markedly lower potency (IC₅₀>0.1mM) at the other cloned GABA transporters (GAT-2, GAT-3, and BGT-1). |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley male rats with partial injury of tail-innervating nerves (neuropathic pain model) |
Preparation Method | Rats that developed robust mechanical allodynia 14 days after nerve injury were administered NNC 711 (20μg/rat) intrathecally via lumbar puncture. Pain behavior (mechanical allodynia) was assessed 30 minutes after drug administration. |
Dosage form | 20μg/rat; intrathecal injection; single injection. |
Applications | Intrathecal administration of NNC 711 significantly attenuated nerve injury-induced mechanical allodynia in neuropathic rats at 30 minutes post-injection. |
References: | |
| Cas No. | 145645-62-1 | SDF | |
| 别名 | NO-711 hydrochloride | ||
| 化学名 | 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid hydrochloride | ||
| Canonical SMILES | OC(C1=CCCN(CCO/N=C(C2=CC=CC=C2)\C3=CC=CC=C3)C1)=O.Cl | ||
| 分子式 | C21H22N2O3.HCl | 分子量 | 386.88 |
| 溶解度 | DMSO: soluble; Water: 10 mM | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5848 mL | 12.9239 mL | 25.8478 mL |
| 5 mM | 517 μL | 2.5848 mL | 5.1696 mL |
| 10 mM | 258.5 μL | 1.2924 mL | 2.5848 mL |
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