Fluoxetine (LY-110140)
(Synonyms: 氟西汀; LY-110140 free base) 目录号 : GC33715
氟西汀Fluoxetine (LY-110140)是一种具有口服活性的选择性5-羟色胺再摄取抑制剂（SSRI）。氟西汀是大鼠和人血小板中饱和[3H]-5-HT摄取过程的强效抑制剂，IC50值分别为0.10和0.05 μM。
Cas No.:54910-89-3
Sample solution is provided at 25 µL, 10mM.
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Cell experiment [1]: |
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Cell lines |
BrdU positive cells |
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Preparation method |
Chronic olanzapine (OLZ) or fluoxetine (LY-110140) (FLX) administration increases the number of bromodeoxyuridine (BrdU)-labeled cells in the dentate gyrus of adult hippocampus. Rats were administered OLZ (5 or 2mg/kg), fluoxetine (5 mg/kg), or the combination of OLZ + fluoxetine. respectively once daily for 21 days. Rats were administered BrdU (150mg/kg) 3 hours after the last drug treatment and killed 24 hours later for BrdU immunohistochemical analysis. |
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Reaction Conditions |
5 mg/kg; 21 days |
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Applications |
Fluoxetine(LY-110140) increases the number of new cells in the dentate gyrus of the hippocampus and the number of proliferating cells in the anterior cortex of adult rats. |
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Animal experiment [2]: |
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Animal models |
Adult male Sprague–Dawley rats |
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Preparation method |
IS and NS animals were treated as above on Days 1 and 2. On Day 2, the IS animals were divided into two groups. One group (IS+FLX group) was given fluoxetine (10 mg/kg, b.i.d.) on Days 2–8 and the other group (IS group) was given a saline injection on Days 2–8. The dose of fluoxetine was chosen based on pilot studies in the laboratory as the behaviorally effective dose in this paradigm. |
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Dosage form |
10 mg/kg; 2-8 days; b.i.d. |
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Applications |
Fluoxetine(LY-110140) treatment reverses the deficit in escape latency observed in animals exposed to inescapable shock in adult male Sprague-Dawley rats. |
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References: [1] Kodama M, et al. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry. 2004 Oct 15;56(8):570-80. [2] Malberg JE, et al. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003 Sep;28(9):1562-71. |
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Fluoxetine (LY-110140) is an orally active, selective serotonin reuptake inhibitor (SSRI) commonly used to treat a variety of psychiatric disorders such as depression, obsessive-compulsive disorder, and panic disorder. Fluoxetine is a potent inhibitor of the saturable [3H]-5-HT (serotonin) uptake process in rat and human platelets, with IC50 values of 0.10 and 0.05 μM, respectively[1]. It exerts its antidepressant effects by specifically inhibiting the reuptake of serotonin (5-HT) in the central nervous system, thereby increasing the concentration of 5-HT in the brain.
In vitro, Fluoxetine (LY-110140) inhibits the K+ currents in OK cells in a concentration-dependent manner, with an EC50 of 107 (84.8; 129.5) μM[2]. Fluoxetine (LY-110140) (5 mg/kg; for 21 days) increases the number of newborn cells in the dentate gyrus of the hippocampus in adult rats, as well as the number of proliferating cells in the prefrontal cortex[3].
In vivo, subchronic study of Fluoxetine (LY-110140) (10 mg/kg/day, orally) in adult male Wistar rats for 15 days significantly reduced urinary K+ excretion, indicating that fluoxetine has an inhibitory effect on renal epithelial K+ channels[2]. After Fluoxetine (LY-110140) treatment, the observed delay in escape latency in adult male Sprague-Dawley rats was reversed[4]. Furthermore, in SD rats, the combination of Fluoxetine (LY-110140) and olanzapine produced robust, sustained increases in extracellular levels of dopamine and norepinephrine, exceeding the baseline by 361% and 272%, respectively, an effect significantly greater than that of either drug used alone[5].
References:
[1] David T. Wong, Kenneth W. Perry, Frank P. Bymaster, et al. The Discovery of Fluoxetine Hydrochloride (Prozac)[J]. Nature Reviews Drug Discovery volume 4, pages764–774 (2005).
[2] Vieira-Coelho M A ,Fátima. Martel. Inhibition of kidney potassium channels by fluoxetine: In vivo and in vitro studies[J].Fundamental & clinical pharmacology, 2022.
[3] Kodama M, et al. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry. 2004 Oct 15;56(8):570-80.
[4] Malberg JE, et al. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003 Sep;28(9):1562-71.
[5] Zhang W, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology. 2000 Sep;23(3):250-62.
氟西汀Fluoxetine (LY-110140)是一种具有口服活性的选择性5-羟色胺再摄取抑制剂（SSRI），常用于治疗抑郁症、强迫症、恐慌症等多种精神疾病。氟西汀是大鼠和人血小板中饱和[3H]-5-HT摄取过程的强效抑制剂，IC50值分别为0.10和0.05 μM [1]。它通过特异性抑制中枢神经系统中的5-羟色胺（5-HT）再摄取，增加大脑中5-HT的浓度，从而发挥抗抑郁作用。
在体外，氟西汀对OK细胞中的K+电流产生浓度依赖性抑制，EC50为107 (84.8; 129.5)μM[2]。氟西汀（5 mg/kg; 21 days）增加成年大鼠的海马的齿状回的新生细胞的数量，也增加了前度皮质的增殖细胞的数目[3]。
在体内，氟西汀（10 mg/kg/d/，p.o.）对雄性成年Wistar大鼠进行亚慢性研究15天，可显著降低尿K+排泄，说明氟西汀对肾上皮K+通道具有抑制作用[2]。氟西汀治疗后，逆转了成年雄性Sprague-Dawley大鼠中观察到的逃避潜伏延迟问题[4]。此外，在SD大鼠中，氟西汀和奥氮平联用产生稳健持续的细胞外多巴胺水平和去甲肾上腺素的增加，超过基准达361％和272％，效果显著大于两种药物单独使用[5]。
| Cas No. | 54910-89-3 | SDF | |
| 别名 | 氟西汀; LY-110140 free base | ||
| Canonical SMILES | FC(C1=CC=C(OC(C2=CC=CC=C2)CCNC)C=C1)(F)F | ||
| 分子式 | C17H18F3NO | 分子量 | 309.33 |
| 溶解度 | 12.5mg/mL in DMSO, 16mg/mL in DMF, 12.5mg/mL in Ethanol | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2328 mL | 16.164 mL | 32.3279 mL |
| 5 mM | 0.6466 mL | 3.2328 mL | 6.4656 mL |
| 10 mM | 0.3233 mL | 1.6164 mL | 3.2328 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Fluoxetine
N Engl J Med 1994 Nov 17;331(20):1354-61.PMID:7935707DOI:10.1056/NEJM199411173312008.
Fluoxetine was developed as an antidepressant drug. It is more effective than placebo, but a dose-effect relation has not been established. Fluoxetine is almost as effective as tricyclic antidepressant drugs, but the available studies do not allow accurate comparisons. Fluoxetine may be less effective than tricyclic antidepressant drugs for the treatment of inpatients with severe melancholic depression, and it should not be the first choice of a drug for them. Fluoxetine may be most appropriate for patients with moderate depression who can be treated as outpatients. If there is little improvement after treatment for four to six weeks, an alternative treatment should be offered. Fluoxetine does not have the anticholinergic, hypotensive, and sedative effects of tricyclic antidepressant drugs and has no particular cardiovascular effects; overdoses do not cause serious toxic effects. Nausea, anorexia, insomnia, and nervousness--the most common side effects--may be controlled with a careful adjustment to the dose. Clinically important drug interactions may occur with monoamine oxidase inhibitors, tricyclic antidepressant drugs, and other drugs. The published data on the antidepressant effect of Fluoxetine do not fully explain its popularity. One may speculate that Fluoxetine has psychobiologic effects not strictly related to the biology of depression and that it acts primarily as a mood- or affect-modulating agent.
Fluoxetine: a case history of its discovery and preclinical development
Expert Opin Drug Discov 2014 May;9(5):567-78.PMID:24738878DOI:10.1517/17460441.2014.907790.
Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as Fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of Fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of Fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on Fluoxetine's effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of Fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved.
Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness
Drugs 1986 Dec;32(6):481-508.PMID:2878798DOI:10.2165/00003495-198632060-00002.
Fluoxetine is a new antidepressant which enhances serotoninergic neurotransmission through potent and selective inhibition of neuronal reuptake of serotonin. Metabolism by N-desmethylation occurs in man yielding desmethylfluoxetine, which also inhibits serotonin reuptake. Both the parent compound and metabolite possess elimination half-lives of several days facilitating the maintenance of steady-state plasma concentrations during long term treatment. Fluoxetine has overall therapeutic efficacy comparable with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients. Geriatric patients also responded as well to Fluoxetine as to doxepin. The symptomatic improvement in patients with unipolar depression during short term Fluoxetine treatment has been satisfactorily maintained when therapy was extended for at least 6 months: the relapse rate was low and similar to that of imipramine. Preliminary data have shown that patients with bipolar depression gained similar therapeutic benefit from Fluoxetine or imipramine. Other preliminary trials have indicated that Fluoxetine may be useful in obsessive-compulsive disorders. Usual doses of Fluoxetine cause significantly fewer anticholinergic-type side effects than tricyclic antidepressants. Nausea, nervousness and insomnia are the most frequently reported fluoxetine-related adverse effects, but these have usually not been severe. Therapeutic doses of Fluoxetine do not affect cardiac conduction intervals in patients without pre-existing cardiovascular disease and Fluoxetine has been relatively safe in the small number of patients who have taken overdoses. It has not been clearly established whether some types of depression may respond more readily to Fluoxetine than other antidepressants, and its overall therapeutic efficacy has not been compared with other second generation antidepressants. Thus, with its different and perhaps improved side effect profile compared with older tricyclic antidepressants, Fluoxetine offers properties that could be used to advantage in many patients with depression.
Prozac (Fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication
Life Sci 1995;57(5):411-41.PMID:7623609DOI:10.1016/0024-3205(95)00209-o.
In this review, we describe the evolutionary process involved in the discovery of the selective 5-HT uptake inhibitor, Fluoxetine, and summarize some of the large body of scientific research performed on Fluoxetine in the 20 years since the first publication. The historical background of the proposed involvement of 5-HT in psychiatric disorders and the activity of tricyclic antidepressants in depression is reviewed. The effects of Fluoxetine in various in vitro assays and in animal studies including receptor down-regulation, neurochemical and behavioral models are summarized. In addition, the clinical effectiveness of Fluoxetine in depression and obsessive compulsive disorders and its potential use in other disorders are examined.
Case history: the discovery of Fluoxetine hydrochloride (Prozac)
Nat Rev Drug Discov 2005 Sep;4(9):764-74.PMID:16121130DOI:10.1038/nrd1821.
In the early 1970s, evidence of the role of serotonin (5-hydroxytryptamine or 5-HT) in depression began to emerge and the hypothesis that enhancing 5-HT neurotransmission would be a viable mechanism to mediate antidepressant response was put forward. On the basis of this hypothesis, efforts to develop agents that inhibit the uptake of 5-HT from the synaptic cleft were initiated. These studies led to the discovery and development of the selective serotonin-reuptake inhibitor Fluoxetine hydrochloride (Prozac; Eli Lilly), which was approved for the treatment of depression by the US FDA in 1987. Here, we summarize this research and discuss the many challenges that we encountered during the development of Fluoxetine hydrochloride, which has now been widely acknowledged as a breakthrough drug for depression.