Saredutant (SR 48968)
(Synonyms: SR 48968; SR 48968C) 目录号 : GC31143
Saredutant (SR 48968) 是一种选择性（Neurokinin 2） NK2受体拮抗剂，IC50值为0.13nM。
Cas No.:142001-63-6
Sample solution is provided at 25 µL, 10mM.
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Saredutant (SR 48968) is a selective (Neurokinin 2) NK2 receptor antagonist with an IC50 value of 0.13nM[1][2]. The neurokinin 2 receptor (NK2 receptor) belongs to the neurokinin receptor family and is primarily involved in various physiological processes, including smooth muscle contraction, regulation of inflammatory responses, and neurotransmission[3]. Saredutant (SR 48968) modulates these neural activities and consequently influence the occurrence and development of related diseases by antagonizing the NK2 receptor[4].
In vitro, pretreatment of CHO cells with Saredutant (SR 48968) (10-50nM) for 2 minutes before NKA stimulation (1.5-7nM) reversed the NKA-induced increases in intracellular calcium levels in a concentration dependent manner[5].
In vivo, treatment with various doses of Saredutant (SR 48968)(1, 3, and 10mg/kg in FSL, 3mg/kg in the FRL, i.p.)for 14 consecutive days increased social interaction (at 10mg/kg), reduced immobility (at 3 and 10mg/kg), and had no effect on locomotor activity in the Flinders Sensitive Line (FSL) rats, but did not affect any of these variables in the Flinders Resistant Line (FRL) rat when compared with the control rats[6]. Oral treatment Saredutant (SR 48968)(30mg/kg) demonstrated a significant reduction in stress-induced temperature, while the number of punished crossings in the four-plate was increased at all doses tested (3–30mg/kg) in the stress-induced hyperthermia (SIH) model[7].
References:
[1] Emonds-Alt, X., Advenier, C., Croci, T., Manara, L., Neliat, G., Poncelet, M., Proietto, V., Santucci, V., Soubrié, P., & Van Broeck, D. (1993). SR 48968, a neurokinin A (NK2) receptor antagonist. Regulatory peptides, 46(1-2), 31–36.
[2] Qi, H., Shah, S. K., Cascieri, M. A., Sadowski, S. J., & MaCcoss, M. (1998). L-tryptophan urea amides as NK1/NK2 dual antagonists. Bioorganic & medicinal chemistry letters, 8(16), 2259–2262.
[3] Quartara, L., Rovero, P., & Maggi, C. A. (1995). Peptide-based tachykinin NK2 receptor antagonists. Medicinal research reviews, 15(2), 139–155.
[4] Hopkins C. R. (2010). ACS chemical neuroscience molecule spotlight on Saredutant. ACS chemical neuroscience, 1(10), 653–654.
[5] Ahlstedt, I., Engberg, S., Smith, J., Perrey, C., Moody, A., Morten, J., Lagerström-Fermér, M., Drmota, T., von Mentzer, B., Påhlman, I., & Lindström, E. (2008). Occurrence and pharmacological characterization of four human tachykinin NK2 receptor variants. Biochemical pharmacology, 76(4), 476–481.
[6] Overstreet, D. H., Naimoli, V. M., & Griebel, G. (2010). Saredutant, an NK2 receptor antagonist, has both antidepressant-like effects and synergizes with desipramine in an animal model of depression. Pharmacology, biochemistry, and behavior, 96(2), 206–210.
[7] Rogacki, N., Lopez-Grancha, M., Naimoli, V., Potestio, L., Stevens, R. J., Pichat, P., Bergis, O. E., Cohen, C., Varty, G. B., & Griebel, G. (2011). The neurokinin NK2 antagonist, saredutant, ameliorates stress-induced conditions without impairing cognition. Pharmacology, biochemistry, and behavior, 98(3), 405–411.
Saredutant (SR 48968) 是一种选择性（Neurokinin 2） NK2受体拮抗剂，IC50值为0.13nM[1][2]。神经激肽2受体（NK2受体）属于神经激肽受体家族，主要参与各种生理过程，包括平滑肌收缩、炎症反应调节和神经传递[3]。Saredutant （SR 48968）通过拮抗NK2受体调节这些神经活动，从而影响相关疾病的发生和发展[4]。
在体外，在NKA刺激（1.5-7nM）之前，用Saredutant （SR 48968）（10-50nM）预处理CHO细胞2分钟，Saredutant （SR 48968）以浓度依赖的方式逆转了NKA诱导的细胞内钙水平的增加[5]。
体内实验中，Saredutant（SR 48968）以不同剂量（在Flinders敏感系大鼠中为1、3和10mg/kg，腹腔注射；在Flinders抵抗系大鼠中为3mg/kg，腹腔注射）连续给药14天，结果显示：在Flinders敏感系（FSL）大鼠中，10mg/kg Saredutant（SR 48968）增加了社交互动，3和10mg/kg剂量减少了不动时间，但对自主活动没有影响；在Flinders抵抗系（FRL）大鼠中，Saredutant（SR 48968）对上述任何变量均无影响[6]。在应激诱导的高热（SIH）模型中，口服Saredutant（SR 48968）（30mg/kg）显著降低了应激诱导的体温升高，同时在所有测试剂量（3–30mg/kg）下，四板实验中的惩罚性穿越次数增加[7]。
| Cell experiment [1]: | |
Cell lines | CHO cells |
Preparation Method | The cells were incubated with the cytoplasmic Ca2+ indicator Fluo-4(TEFLABS 0152) at 4mM in loading media (Nut Mix F12 (HAM) with Glutamax I, 22mM HEPES, 2.5mM probenicid (Sigma, P-8761) and 0.04% Pluronic F-127 (Sigma P-2443)) for 30minutes in a 37℃ CO2-incubator. The Fluo-4-loaded cells were then washed three times in assay buffer (Hanks Balanced Salt Solution, 20mM HEPES, 2.5mM probenicid and 0.1% BSA). The plates were then placed into the FLIPRTM to monitor cell fluorescence (lex = 488nm, lem = 540nm) before and after the addition of antagonists(Saredutant (SR 48968)) and/or agonists(NKA). Saredutant (SR 48968) and NKA were dissolved in assay buffer (final DMSO concentration kept below 1%) on 96-well plates and added to the loaded cells by the automated pipettor in the FLIPRTM. Loaded cells were pre-incubated with Saredutant (SR 48968) for approximately 2min before addition of NKA at the EC50 for each construct (ranged between 1.5 and 7nM). Intracellular Ca2+ mobilization responses were measured as peak fluorescence intensity after agonist addition minus basal fluorescence. |
Reaction Conditions | 10-50nM; 2min |
Applications | Saredutant (SR 48968) (10-50nM) reversed the NKA-induced increases in intracellular calcium levels in a concentration dependent manner. |
| Animal experiment [2]: | |
Animal models | male FSL and FRL rats |
Preparation Method | The FSL rats (n= 8) were treated with one of the following: vehicle (carboxymethylcellulose — CMC) or 1, 3, or 10mg/kg Saredutant (SR 48968), or 5mg/kg desipramine as a positive control The FRL rats were given CMC or 3mg/kg Saredutant (SR 48968). All injections were i.p. and were given for 14 consecutive days. Approximately 22h after the last injections the rats were placed in the social interaction chamber with similarly treated rats for a 5-min recording. Then about 2h later the rats were individually tested in the forced swim test for a single 5- min session. |
Dosage form | 1,3,10mg/kg/day for 14 days; i.p. |
Applications | Saredutant (SR 48968) increased social interaction (at 10mg/kg) reduced immobility (at 3 and 10mg/kg), and had no effect on locomotor activity in the FSL rats, but did not affect any of these variables in the FRL rat compared with the control rats. |
References: | |
| Cas No. | 142001-63-6 | SDF | |
| 别名 | SR 48968; SR 48968C | ||
| Canonical SMILES | CC(NC1(C2=CC=CC=C2)CCN(CC[C@@H](C3=CC(Cl)=C(Cl)C=C3)CN(C)C(C4=CC=CC=C4)=O)CC1)=O | ||
| 分子式 | C31H35Cl2N3O2 | 分子量 | 552.53 |
| 溶解度 | DMSO: 250 mg/mL (452.46 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8099 mL | 9.0493 mL | 18.0986 mL |
| 5 mM | 0.362 mL | 1.8099 mL | 3.6197 mL |
| 10 mM | 0.181 mL | 0.9049 mL | 1.8099 mL |
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动物数量 | 只 |
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