TC-2559 free base
TC-2559 free base is a α4β2 nicotinic acetylcholine receptor (nAChR) agonists with an EC50 of 0.18 μM. TC-2559 free base shows much weaker potencies on the group of b4-containing nAChR subtypes, α2β4, α4β4 and α3β4 receptors, with EC50s in the range of 10-30 µM. TC-2559 free base can increase the discharge of dopamine cells in the ventral tegmental area (VTA) of rats in vitro, enhancing the excitability and aggressive behavior of VTA dopamine neurons. TC-2559 free base inhibits STAT3 to exert anti-inflammatory properties and relieves mice mechanical allodynia and improve rats cognitive deficits. TC-2559 free base can be used for the study of nerve pain.
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- CAS No.: 189274-78-0
- Formule: C12H18N2O
- Masse moléculaire:206.28
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Activité biologique
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Cell Line
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Type | Value | Description | References |
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| CHO | EC50 |
20 μM
Compound: TC-2559
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Agonist activity at human alpha3beta4 nAChR expressed in CHO cells assessed as calcium flux by calcium4-based FLIPR assay
Agonist activity at human alpha3beta4 nAChR expressed in CHO cells assessed as calcium flux by calcium4-based FLIPR assay
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[PMID: 22793665] |
TC-2559 free base (free base) competes effectively with [3H]-mocotine binding (Ki = 5 nM) [1].
TC-2559 free base (0-100 nM) enhances dopamine release in rat striatal synaptic vesicles (EC50, E
TC-2559 free base (10 μM, 2 h) can significantly reduce neuronal death in the brain cells of fetal mice[1].
TC-2559 free base (200-500 μM, 3-6 h) suppresses the upregulation of CC-chemokine ligand 3 (CCL3) and interleukin-1b (IL-1b) in murine macrophages[3].
TC-2559 free base (500 μM, 1-6 h) inhibits the phosphorylation of signal transducer and activator of transcription 3
(pSTAT3) in murine macrophages[3].
TC-2559 free base (0.5 mM, 24 h) suppresses the upregulation of interleukin-1β (IL-1β) in the injured SCN after PSL in mice peritoneal macrophages[4].
TC-2559 free base shows much weaker potencies on the group of β4-containing nAChR subtypes, α2β4, α4β4 and α3β4 receptors, with EC50s of 14, 12.5 and >30 μM, respectively[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Mouse macrophage J774A.1 cells
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Concentration:20-500 μM with LPS (HY-D1056)
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Incubation Time:3 and 6 h
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Result:Suppressed the mRNA expressions of CCL3 and IL-1b.
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Cell Line:Mouse macrophage J774A.1 cells
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Concentration:500 μM with LPS
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Incubation Time:1,3 and 6 h
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Result:Inhibited the upregulation of pSTAT3 at 6 h. Had no effect on pp65 expression at 1 and 6 h.
HC-2559 (0.124-2.063 mg/kg μmol/kg, s.c., single dose or for 5 days) significantly reduces errors in working memory, and sustainably improves working memory[1].
HC-2559 (0.206-1.238 mg/kg, s.c., single dose or for 14 days) causes motor inhibition at a single administration and does not induce behavioral sensitization after continuous administration[1].
TC-2559 free base (0.021-1.32 mg/kg, i.v., cumulative doses or single dose) activates VTA dopamine neurons through α4β2-like nAChRs[2].
TC-2559 free base (0.47-4.70 mg/kg, s.c. or 20 nmol, perineural Injections, for 3 days) significantly relieves mechanical allodynia in mice behavioral model[4].
TC-2559 free base (20 nmol, perineural Injections, for 3 days) suppresses microglial activation in the SDH induced by peripheral nerve injury in mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Attenuation of scopolamine-induced amnesia established in male Sprague-Dawley rats (200-350 g)[1]
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Dosage:0.124, 0.206, 0.619, 1.238 and 2.063 mg/kg (0.6, 1, 3, 6 and 10 μmol/mg)
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Administration:Subcutaneous Injections (s.c.), single dose
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Result:Attenuated scopolamine-induced decrease of avoidance latencies of 21.5 s at doses of 3 and 6 μmol/kg.
Exhibited the median step-through latencies of 88.7 and 105.7 s for 3 and 6 μmol/kg, respectively.
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Animal Model:Radial-arm maze performance model established in male Sprague-Dawley rats (200-350 g)[1]
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Dosage:0.124, 0.206, 0.619 and 1.238 mg/kg (0.6, 1, 3 and 6 μmol/mg)
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Administration:Subcutaneous Injections (s.c.), single dose or for 5 days
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Result:Significantly reduced the number of working memory errors at 3 and 10 μmol/kg in Day 1.
Significantly reduced working memory errors following 6 days of repeated administration at 1, 3, and 6 μmol/kg.
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Animal Model:Locomotor activity model established in male Sprague-Dawley rats (200-350 g)[1]
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Dosage:0.124, 0.412 and 2.063 mg/kg for acute administration and 0.721 mg/kg for repeated administration
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Administration:Subcutaneous Injections (s.c.), single dose or once daily or for 14 days
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Result:Resulted in significant reductions in horizontal counts at the 30-min time point.
Resulted in a dose-dependent monophasic change in locomotor behavior with a sustained hypolocomotion at 60 min for the 0.206 mg/kg dose.
No apparent sensitization developed following repeated administration.
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Animal Model:Electrophysiological model established in male Sprague-Dawley rats (260-350 g)[2]
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Dosage:0.021-1.32 mg/kg or 0.66 and 1.32 mg/kg
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Administration:Intravenous injection (i.v.), cumulative doses or single dose
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Result:Increased the discharge frequency by 185%-206%.
Increased the peak discharge frequency to 141% at 0.66 mg/kg.
induced bursting in one of two nonbursting VTA DA neurones tested.
Evoked a significant increase in both spontaneous and burst firing for up to 15 min of the testing period at 1.32 mg/kg.
Were blocked by DHbE, but not by MLA.
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Animal Model:Behavioral testing in male ICR mice aged 4 to 5 weeks[4]
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Dosage:0.470, 1.41 and 4.70 mg/kg (2.28, 6.84 and 22.8 μmol/kg) (s.c.) or 20 nmol (p.n.)
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Administration:Subcutaneous Injections (s.c.) or perineural Injections (p.n.) for 3 days
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Result:Significantly increase the mechanical pain threshold at 22.8 μmol/kg during either the early (days 0–3) or middle/late (days 7–10).
Improved mechanical allodynia with Sazetidine A (HY-14319A) with p.n. admisitraion during the early or middle phase.
Relieved mechanical allodynia with p.n. during the late (days 21-24) phase.
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Animal Model:Microglial activation assay in male ICR mice aged 4 to 5 weeks[4]
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Dosage:20 nmol
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Administration:Perineural Injections (p.n.) for 3 days
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Result:Suppressed microglial activation in the SDH evaluated by Iba1 expression.
Significantly down-regulate inflammatory markers such as CD68, IRF5, and IL-1β.
Chemical Information
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CAS No. 189274-78-0
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Masse moléculaire 206.28
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Formule C12H18N2O
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SMILES
CNCC/C=C/C1=CN=CC(OCC)=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Bencherif M, et al. TC-2559: a novel orally active ligand selective at neuronal acetylcholine receptors. Eur J Pharmacol. 2000 Dec 1;409(1):45-55. [Content Brief]
[2]. Wang Y, et al. TC-2559 excites dopaminergic neurones in the ventral tegmental area by stimulating alpha4beta2-like nicotinic acetylcholine receptors in anaesthetised rats. Br J Pharmacol. 2006 Feb;147(4):379-90. [Content Brief]
[3]. Kiguchi N,et al. TC-2559, an α4β2 nicotinic acetylcholine receptor agonist, suppresses the expression of CCL3 and IL-1β through STAT3 inhibition in cultured murine macrophages. J Pharmacol Sci. 2015 Jun;128(2):83-6. [Content Brief]
[4]. Kiguchi N, et al. Inhibition of peripheral macrophages by nicotinic acetylcholine receptor agonists suppresses spinal microglial activation and neuropathic pain in mice with peripheral nerve injury. J Neuroinflammation. 2018 Mar 27;15(1):96. [Content Brief]
[5]. Chen Y, et al. The nicotinic alpha 4 beta 2 receptor selective agonist, TC-2559, increases dopamine neuronal activity in the ventral tegmental area of rat midbrain slices. Neuropharmacology. 2003 Sep;45(3):334-44. [Content Brief]
Calculators
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TC-2559 free base Related Classifications
HY-171807 Related Classifications
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