NS3956
NS3956 is a blood-brain barrier-permeable human α4β2-nicotinic acetylcholine receptor (nAChR) agonist (Ki = 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.
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- No. CAS: 223796-90-5
- Fòrmula: C10H14ClN3
- Peso molecular:211.69
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Chemical Information
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Actividad biológica
Descripciòn
In Vitro
NS3956 binds with high affinity and selectivity to α4β2-nAChRs (Ki = 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 Ki value of 399 nM[2].
NS3956 binds to α1-nAChRs in human TE671 medulloblastoma cell membranes, with a Ki 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.
In Vivo
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.
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Animal Model:NMRI mice (female, 18-23 weeks old, 25-30 g)[2]
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Dosage:0.3 mg/kg; 1.0 mg/kg; 3.0 mg/kg
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Administration:s.c.; single dose
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Result:Showed no notable changes in forced swim distance (557.8 cm, 665.4 cm, 603.5 cm) relative to vehicle (564.6 cm) and no meaningful shift in tail suspension immobility time after solo administration.
Potentiated subthreshold 3 mg/kg citalopram to raise swim distance versus single NS3956 or single citalopram upon combination.
Strengthened 10 mg/kg reboxetine to increase swim distance against standalone NS3956 or standalone reboxetine, and boosted 20 mg/kg reboxetine’s effect vs single NS3956 in co-treatment.
Elevated locomotor activity vs vehicle when given alone.
Increased locomotor activity relative to single 10 mg/kg citalopram with combined citalopram dosing.
Decreased locomotor activity compared with solitary NS3956 following co-administration with 10 mg/kg reboxetine.
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Animal Model:Sprague Dawley (adult female, 6-OHDA lesion of right nigrostriatal pathway)[3]
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Dosage:1 mg/kg; 3 mg/kg (alone)
0.1 mg/kg; 0.3 mg/kg; 1 mg/kg (co-administered with nomifensine)
0.3 μg/kg; 3 μg/kg; 10 μg/kg (co-administered with NS9283) -
Administration:s.c. (alone, co-administered with NS9283); i.p. (co-administered with nomifensine)
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Result:Exerted non-significant dose-related rises in rotational behaviour upon single administration.
Elevated rotational behaviour markedly, with evident efficacy at 0.3 mg/kg versus vehicle after combined nomifensine treatment.
Suppressed rotational behaviour significantly starting at 3 μg/kg versus vehicle, with 3 μg/kg defined as the lowest effective inhibitory dose in combination with NS9283.
Chemical Information
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No. CAS 223796-90-5
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Peso molecular 211.69
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Fòrmula C10H14ClN3
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SMILES
ClC1=CN=CC(N2CCNCCC2)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[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. [Content Brief]
[3]. Rode F, et al. Positive allosteric modulation of α4β2 nAChR agonist induced behaviour. Brain Res. 2012;1458:67-75. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NS3956 Related Classifications
HY-183666 Related Classifications
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Keywords
- NS3956
- 223796-90-5
- NS 3956
- NS-3956
- nAChR
- Serotonin Transporter
- Xenopus laevis oocytes
- major depressive disorder
- human α7 nAChRs
- 6-OHDA lesioned rats
- human α4β2-nicotinic acetylcholine receptor
- human TE671 medulloblastoma cell membranes
- dopamine
- Sprague Dawley rats
- human α3β4 nAChRs
- rat α4β2-nAChR
- Inhibitor
- inhibitor
- inhibit