SA 4503 dihydrochloride

Names

[ Name ]:
SA 4503 dihydrochloride

[Synonym ]:
1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine,dihydrochloride
1-(3,4-Dimethoxyphenethyl)-4-(3-phenylpropyl)piperazinedihydrochloride
Piperazine, 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)-, hydrochloride (1:2)
1-[2-(3,4-Dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
SA-4503
SA4503 2HCl
SA4503 (dihydrochloride)

Biological Activity

[Description]:

Cutamesine dihydrochloride (SA4503 dihydrochloride) is a potent Sigma 1 receptor agonist with an IC50 of 17.4 nM in guinea pig brain membranes.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Sigma Receptor

Research Areas >> Neurological Disease

[Target]

IC50: 17.4 nM (σ1receptor, guinea pig brain membranes)[1]

[In Vitro]

The sigma receptor might be involved in several diseases in the central nervous system. Cutamesine, a potent σ1receptor agonist, has 103-fold higher affinity for σ1 (IC50=17.4 nM) than σ2 (IC50=1,784 nM) sites in guinea pig brain membranes. Cutamesine is 14-fold selective for σ1 (Ki=4.6 nM) over σ2 (Ki=63.1 nM) sites in guinea pig brain homogenates[1]. Cutamesine protects motor neuron NSC34 cells against superoxide dismutase 1 and serum free neurotoxicity. It upregulates the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) 1/2[2]. Cutamesine reduces the activation of the MAPK/ERK pathway and down-regulated the ionotropic glutamate receptor, GluR1[3].

[In Vivo]

Cutamesine extends the survival time in the SOD1G93A mice[2].

[Cell Assay]

The NSC34 cells are seeded at a density of 7000 cells per well into 96-well plates with D-MEM and transfected using Lipofectamine 2000 mixed with 2 μg /mL of plasmid vector in D-MEM for 6 h. After 6 h, the cell-culture medium is replaced with fresh D-MEM and culture and allowed to proceed for a further 42 h. The cells are then transferred to serum-free D-MEM and immediately treated with Cutamesine at a final concentration of 1, 3, or 10 nM[2].

[Animal admin]

Mice: Transgenic female mice overexpressing mutated human SOD1G93A are used in the study. Cutamesine is dissolved in saline and subcutaneously administered at a dose of 1 mg/kg once daily to 5-week-old SOD1G93A mice to the time of death. In a control group, vehicle (saline) is subcutaneously administered at 10 ml/kg[2].

[References]

[1]. Lever JR, et al. Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503. Synapse. 2006 May;59(6):350-8.

[2]. Tuerxun T, et al. SA4503, a sigma-1 receptor agonist, prevents cultured cortical neurons from oxidative stress-induced cell death via suppression of MAPK pathway activation and glutamate receptor expression. Neurosci Lett. 2010 Jan 29;469(3):303-8.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
499.2ºC at 760 mmHg

[ Molecular Formula ]:
C₂₃H₃₄Cl₂N₂O₂

[ Molecular Weight ]:
441.434

[ Flash Point ]:
137.3ºC

[ Exact Mass ]:
440.199738

[ PSA ]:
24.94000

[ LogP ]:
4.97650

[ Vapour Pressure ]:
4.25E-10mmHg at 25°C

Safety Information

[ HS Code ]:
2933599090

Customs

[ HS Code ]: 2933599090

[ Summary ]:
2933599090. other compounds containing a pyrimidine ring (whether or not hydrogenated) or piperazine ring in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%