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Fluoxetine HCl

现货
Catalog No.
A2436
5-羟色胺重吸收抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
现货
100mg
¥ 850.00
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500mg
¥ 2,400.00
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Background

Fluoxetine is a specific presynaptic serotonin-reuptake inhibitor (SSRI) at the neuronal membrane, used in the treatment of depression.

The serotonin receptor, also known as 5-HT receptor, is a member of G protein-coupled receptorfound in the central and peripheral nervous systems. The serotonin receptors, activated by the natural ligand serotonin,have been involved in a variety of biological and neurological processes such as aggression, anxiety, cognition, learning, memory, mood[1].

In vitro:In Xenopusoocytes expressing either cloned 5HT2C receptors or 5HT receptors, micromolar concentrations of fluoxetine (Prozac) inhibited the membrane currents elicited by serotonin (5-hydroxytryptamine; 5HT). For responses elicited by 1 μM 5-HT, the IC50 of fluoxetine was about 20 μM. Fluoxetine also inhibited the binding of [3H]5HT to 5HT2C receptors expressed in HeLa cells and the binding of [3H]5HT to 5HT receptors in rat cortex membranes, with Ki of ≈65–97 nM and ≈ 56 μM, respectively[2]. Administration of fluoxetine blocked the downregulation of cell proliferation of hippocampal cells resulting from inescapable shock (IS), which resulted in a state of behavioral despair[3]. Fluoxetine increased the number of newborn cells in the dentate gyrus of the hippocampus of adult rat. Fluoxetine also increased the number of proliferating cells in the prelimbic cortex[4]. Fluoxetine accelerated the maturation of immature neurons. Fluoxetine enhanced neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus [5]. Fluoxetine, but not other selective serotonin uptake inhibitors such as citalopram, fluvoxamine, paroxetine and sertraline, increased norepinephrine and dopamine extracellular levels in prefrontal cortex. Fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration [6].

In vivo: Fluoxetine reversed the deficit in escape latency observed in animals exposed to inescapable shock in adult male Sprague–Dawley rats [3].The combination of olanzapine and fluoxetine produced robust, sustained increases of extracellular levels of dopamine ([DA](ex)) and norepinephrine ([NE](ex)) up to 361 ± 28% and 272 ± 16% of the baseline, respectively[7]. Fluoxetine (5 and 10 mg/kg) reduced cocaine infusions (0.2 mg/kg), and cocaine infusions returned to baseline levels within 48 hr after fluoxetine treatments were terminated [8]. In sham-operated or adrenalectomized/castrated (ADX/CX) male rats, administration of fluoxetine dose-dependently (2.9-58 mumol/kg i.p.) increased the brain content of the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, 3 alpha, 5 alpha-TH PROG)[9].

Clinical trials: In a 5-wk double-blind, parallel study with 40 depressed 23–69 yr olds, fluoxetine(20–80 mg/day) provided effective antidepressant activity, with fewer and less side effects[10].

References:
[1]. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994)."International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)".Pharmacol. Rev.46(2): 157–203.
[2]. Ni Y G, Miledi R. Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac)[J]. Proceedings of the National Academy of Sciences, 1997, 94(5): 2036-2040.
[3]. Malberg J E, Duman R S. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment[J]. Neuropsychopharmacology, 2003, 28(9): 1562-1571.
[4]. Kodama M, Fujioka T, Duman R S. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat[J]. Biological psychiatry, 2004, 56(8): 570-580.
[5]. Wang J W, David D J, Monckton J E, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells[J]. The Journal of neuroscience, 2008, 28(6): 1374-1384.
[6]. Bymaster F P, Zhang W, Carter P A, et al. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex[J]. Psychopharmacology, 2002, 160(4): 353-361.
[7]. Zhang W, Perry K W, Wong D T, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex[J]. Neuropsychopharmacology, 2000, 23(3): 250-262.
[8]. Carroll M E, Lac S T, Asencio M, et al. Fluoxetine reduces intravenous cocaine self-administration in rats[J]. Pharmacology Biochemistry and Behavior, 1990, 35(1): 237-244.
[9].  (Uzunov D P, Cooper T B, Costa E, et al. Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography[J]. Proceedings of the National Academy of Sciences, 1996, 93(22): 12599-12604.
[10]. Bremner J D. Fluoxetine in depressed patients: a comparison with imipramine[J]. Journal of Clinical Psychiatry, 1984.

Chemical Properties

StorageStore at -20°C
M.Wt345.79
Cas No.56296-78-7
FormulaC17H18F3NO.HCl
Solubility≥17.3mg/mL in DMSO
Chemical NameN-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine;hydrochloride
SDFDownload SDF
Canonical SMILESCNCCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

表达5HT2C受体或5HT受体的爪蟾卵母细胞

溶解方法

在DMSO中的溶解度> 17.3 mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

100 μM

应用

在表达5HT2C受体或5HT受体的爪蟾卵母细胞中,fluoxetine抑制由5-羟色胺引起的膜电流。微摩尔浓度的fluoxetine可以快速并可逆地阻断纳摩尔浓度的5HT引起的5HT2c受体响应。根据电生理结果,fluoxetine抑制[3H]5HT与5HT2c受体的结合,也抑制[3H]5HT与大鼠皮质膜上的5HT受体结合,但抑制效果稍微弱一些。

动物实验 [2]:

动物模型

雄性SD大鼠

剂量

5 mg/kg/day,腹腔注射

应用

奥氮平(Olanzapine)或者氟西汀(fluoxetine)治疗能够增加前边缘皮层中增殖细胞的数量。相比之下,两个药对于脑室下区或者初级运动皮层的细胞未有影响。亚长期(7天)的奥氮平治疗对于海马区或者前边缘皮层的细胞增殖不产生影响,这也与氟西汀的效果以及抗抑郁治疗的机理一致。此外,联合奥氮平以及氟西汀治疗也并不能带来更好的诱导脑区细胞增殖的效果。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Ni Y G, Miledi R. Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac)[J]. Proceedings of the National Academy of Sciences, 1997, 94(5): 2036-2040.

[2] Kodama M, Fujioka T, Duman R S. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat [J]. Biological psychiatry, 2004, 56(8): 570-580.

质量控制

化学结构

Fluoxetine HCl