NS-6740 is a silent agonist of α7 nicotinic acetylcholine receptor ( α7 nAChR ) with an IC50 of 3 nM. NS-6740 reduces LPS-induced TNF-α release and regulates the cholinergic anti-inflammatory pathway. NS-6740 exerts anti-inflammatory effects. NS-6740 reduces long-term potentiation in hippocampal brain slices. NS-6740 can be used in research related to neuroinflammation and schizophrenia [1] [2] [3].
In Vivo, NS-6740 (10 mg/kg; s.c.; single dose), at a dose achieving 98% α7 nAChR occupancy, blocks the memory-improving effects of BMS-933043 in the mouse novel object recognition task[3]. NS-6740 (3-10 mg/kg; s.c.; single dose), at doses achieving 89% and 98% α7 nAChR occupancy, does not enhance memory retention in the mouse novel object recognition task[3].
In Vitro, NS-6740 (0.01-100 μM; 30 min) potently inhibits LPS-induced TNF-α release in enriched primary rat microglial cultures, achieving complete inhibition at concentrations of 50 and 100 μM. Co-treatment with a partial α7 nAChR agonist enhances this effect, which is not mediated by regulation of the MAPK pathway[1]. NS-6740 (5 μM; 60 s) induces persistent desensitization of α7 nAChR expressed in Xenopus laevis oocytes, and the desensitized receptors can be activated by the positive allosteric modulator PNU-120596 [2]. NS-6740 acts as an antagonist of the recombinant 5-HT3A receptor expressed in HEK293 cells, with an IC50 value of 4827 nM[3]. NS-6740 binds to native rat α7 nAChR with high affinity, with a Ki value of 2.85 nM[3]. NS-6740 inhibits the activation of recombinant rat α7 nAChRs expressed in HEK293 cells induced by BMS-933043, with an IC50 value of 283 nM for peak current and 255 nM for net charge[3].
References:
[1]. Thomsen MS, et al. The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia. Journal of neuroimmunology. 2012 Oct 15;251(1-2):65-72.
[2]. Papke RL, et al. NS6740, an α7 nicotinic acetylcholine receptor silent agonist, disrupts hippocampal synaptic plasticity. Neuroscience letters. 2018 Jun 11;677:6-13.
[3]. Bristow LJ, et al. The Novel, Nicotinic Alpha7 Receptor Partial Agonist, BMS-933043, Improves Cognition and Sensory Processing in Preclinical Models of Schizophrenia. PloS one. 2016;11(7):e0159996.
In Vivo, NS-6740 (10 mg/kg; s.c.; single dose), at a dose achieving 98% α7 nAChR occupancy, blocks the memory-improving effects of BMS-933043 in the mouse novel object recognition task[3]. NS-6740 (3-10 mg/kg; s.c.; single dose), at doses achieving 89% and 98% α7 nAChR occupancy, does not enhance memory retention in the mouse novel object recognition task[3].
In Vitro, NS-6740 (0.01-100 μM; 30 min) potently inhibits LPS-induced TNF-α release in enriched primary rat microglial cultures, achieving complete inhibition at concentrations of 50 and 100 μM. Co-treatment with a partial α7 nAChR agonist enhances this effect, which is not mediated by regulation of the MAPK pathway[1]. NS-6740 (5 μM; 60 s) induces persistent desensitization of α7 nAChR expressed in Xenopus laevis oocytes, and the desensitized receptors can be activated by the positive allosteric modulator PNU-120596 [2]. NS-6740 acts as an antagonist of the recombinant 5-HT3A receptor expressed in HEK293 cells, with an IC50 value of 4827 nM[3]. NS-6740 binds to native rat α7 nAChR with high affinity, with a Ki value of 2.85 nM[3]. NS-6740 inhibits the activation of recombinant rat α7 nAChRs expressed in HEK293 cells induced by BMS-933043, with an IC50 value of 283 nM for peak current and 255 nM for net charge[3].
References:
[1]. Thomsen MS, et al. The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia. Journal of neuroimmunology. 2012 Oct 15;251(1-2):65-72.
[2]. Papke RL, et al. NS6740, an α7 nicotinic acetylcholine receptor silent agonist, disrupts hippocampal synaptic plasticity. Neuroscience letters. 2018 Jun 11;677:6-13.
[3]. Bristow LJ, et al. The Novel, Nicotinic Alpha7 Receptor Partial Agonist, BMS-933043, Improves Cognition and Sensory Processing in Preclinical Models of Schizophrenia. PloS one. 2016;11(7):e0159996.