NS3956 

NS3956 is a blood-brain barrier-permeable human α4β2-nicotinic acetylcholine receptor (nAChR) agonist (K_i = 0.36 nM). NS3956 induces dopamine release, produces analgesic effects, modulates rotational behavior in 6-OHDA-lesioned rats, and potentiates the effects of SSRI/SNRI in the forced swim test in mice. NS3956 can be used in research related to depression, Parkinson's disease, and acute pain^[1][2][3].

NS3956 binds with high affinity and selectivity to α4β2-nAChRs (K_i = 0.36 nM) relative to human α7 and α1-nAChRs, and does not interact significantly with monoamine transporters^[1][2].
NS3956 acts as a partial agonist at human HS α4β2-nAChRs (EC₅₀ = 11 nM) and LS α4β2-nAChRs (EC₅₀ = 604 nM) expressed in Xenopus oocytes^[1].
NS3956 acts as a full agonist at human α7-nAChRs expressed in Xenopus laevis oocytes, with an EC₅₀ of 26 μM^[2].
NS3956 binds to α7-nAChRs in rat cortical membranes, with a K_i value of 399 nM^[2].
NS3956 binds to α1-nAChRs in human TE671 medulloblastoma cell membranes, with a K_i value of 944 nM^[2].
NS3956 inhibited the uptake of serotonin in rat cerebral cortex specimens, with an IC50 of 3930 nM; it did not show any inhibitory activity against norepinephrine or dopamine uptake^[2].
NS3956 acts as a partial agonist on both HS and LS α4β2 nAChRs with EC₅₀ values of 11 nM and 604 nM, respectively, and has limited off-target activity at other nAChR subtypes and monoamine transporters^[3].
NS3956 induces concentration-dependent dopamine release from rat striatal minces with an EC₅₀ of 0.43 μM, an effect mediated by nAChRs^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

NS3956 (0.3-3 mg/kg; s.c.; single dose) alone shows no antidepressant-like activity in the mouse forced swim or tail suspension tests, but 1.0 mg/kg NS3956 significantly enhances the antidepressant-like effects of subthreshold doses of Citalopram (HY-121203) and Reboxetine (HY-14560) in the mouse forced swim test^[2].
NS3956 (0.001-3 mg/kg; s.c.; single dose) crosses the blood-brain barrier and engages central α4β2 nicotinic acetylcholine receptors with an ED₅₀ of 0.033 mg/kg s.c^[2].
NS3956 (1-3 mg/kg; 0.3 μg/kg-10 μg/kg; s.c.; i.p.) non-significantly increases rotational behaviour alone, significantly increases rotational behaviour at a dose of 0.3 mg/kg when co-administered with Nomifensine (HY-B1110), and significantly inhibits rotational behaviour at a dose of 3 μg/kg when co-administered with NS9283 (HY-110168) in 6-OHDA-lesioned female Sprague Dawley rats^[3].
NS3956 (1-10 mg/kg; 0.03-1 mg/kg; s.c.) significantly reduces formalin-induced flinching behaviour at doses of 1 mg/kg (first phase) and 3 mg/kg (second phase) when administered alone, and demonstrates a 100-fold increase in antinociceptive potency when co-administered with NS9283 in male Sprague Dawley rats^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

211.69

C₁₀H₁₄ClN₃

223796-90-5

ClC1=CN=CC(N2CCNCCC2)=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Yu LF, et al. Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors. J Med Chem. 2014;57(20):8204-8223.  [Content Brief]

  [2]. Andreasen JT, et al. Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test. J Psychopharmacol. 2011;25(10):1347-1356.

  [3]. Rode F, et al. Positive allosteric modulation of α4β2 nAChR agonist induced behaviour. Brain Res. 2012;1458:67-75.