Na+/2Cl-/K+ (NKCC) symporter; NKCC1/2; GABAA receptors

当低分化人胃癌细胞系 MKN45 接触呋塞米 (500 µM) 72-96 小时后，其增殖率会出现相当大的变化。另一方面，MKN28 细胞（一种中等分化的人胃腺癌细胞系）未受影响。与 MKN28 细胞相比，MKN45 细胞发育速度更快 [4]。在健康人的红细胞中，呋塞米（10 µM、30 µM 和 100 µM；暴露 45 分钟）可显着降低 [Ca(2+)](i) 和阳离子通道活性。叔丁基过氧化氢对非选择性阳离子通道活性、[Ca(2+)](i) 和细胞膜破坏也有类似的影响；然而，呋塞米也显着降低了这些影响[5]。

为了创建耳聋小鼠模型，将卡那霉素 (KM) (1000 mg/kg) 和呋塞米（腹腔注射；100 mg/kg；单剂量）注射到 C57BL/6 小鼠中。在注射后的第 1、2 和 3 天，相应地测量了听力损失和耳蜗毛细胞破坏情况。第3天，动物的上、中、下转的OHC（外毛细胞）形态出现异常，听力从第2天（第1天组）开始就已经严重下降[3]。

小脑颗粒细胞中的GABAA受体在表达含有alpha6亚基的亚型方面是独一无二的。这种受体亚型对GABA有高亲和力，对小脑颗粒细胞产生一定程度的强直抑制，通过GABA从GABA能突触溢出来调节这些细胞的放电。与含有其他α亚基的受体相比，该受体亚型对利尿剂Furosemide/速尿也具有选择性亲和力。速尿对含alpha6受体的选择性约为含alpha1受体的100倍。通过制造alpha1/alpha6嵌合体，我们已经确定了一个跨膜区域(209-279)，负责alpha6beta3gamma2s受体的高速尿敏感性。在α - 1跨膜区，发现了一个氨基酸，当从苏氨酸突变为异亮氨酸时，将Furosemide/速尿敏感性提高了20倍。我们证明了呋塞米的β亚基选择性是由于β 2和β 3跨膜结构域II中的天冬酰胺265，这与抗惊厥药氯来唑增强所观察到的相似。我们还发现，与alpha1beta3gamma2s受体相比，跨膜结构域I中的Ile可以解释在alpha6beta3gamma2s受体上观察到的GABA敏感性增加，但不影响戊巴比妥的直接激活或苯二氮卓类氟西泮的增强作用。这些残基在跨膜结构域中的位置导致人们猜测它们可能参与通道门控机制，除了赋予速尿敏感性外，还赋予GABA增加受体激活。[2]

Furosemide/速尿是一种Na(+)/K(+)/2Cl(-)共转运体(NKCC)阻滞剂，常作为利尿剂用于改善癌症患者的水肿、腹水和胸腔积液。本研究的目的是研究NKCC阻滞剂是否会影响癌细胞的生长。如果是这样，我们将澄清这一行动的机制。我们发现，低分化胃癌细胞(MKN45)表达NKCC1 mRNA的水平是中等分化胃癌细胞(MKN28)的3倍，且MKN45中的NKCC活性高于MKN28。细胞增殖试验表明，速尿显著抑制MKN45细胞的细胞生长，而对MKN28细胞无抑制作用。通过流式细胞术分析，我们发现暴露于速尿使MKN45细胞在G(0)/G(1)期停留的时间更长，而MKN28细胞则没有。基于这些观察结果，我们发现速尿通过延缓NKCC高表达和活性的低分化胃腺癌细胞的G(1)-S期进展来减缓细胞生长，但在低表达和NKCC活性的中分化胃腺癌细胞中则没有这种作用[1]。

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背景:Furosemide/速尿是一种抑制肾小管Na(+)、K(+)、2Cl(-)共转运体的环状利尿剂，已被证明可降低血小板和红细胞中胞浆Ca(2+)浓度([Ca(2+)](i))。红细胞中的[Ca(2+)](i)是Ca(2+)渗透阳离子通道的功能。这些通道的激活，例如能量消耗或氧化应激导致[Ca(2+)](i)的增加，这反过来引发红细胞凋亡，这是一种以细胞膜混乱为特征的自杀性红细胞死亡。本研究旨在探讨速尿是否会影响阳离子通道，从而影响脓毒症[5]。
方法:采用全细胞膜片钳法测定阳离子通道活性，[Ca(2+)](i)利用Fluo3荧光和膜联蛋白V结合来估计磷脂酰丝氨酸暴露时细胞膜的混乱。[5]
结果:暴露于速尿(10和100µM) 45分钟，轻微但显著降低健康人红细胞的阳离子通道活性和[Ca(2+)](i)。atp耗竭(> 3小时，+37°C, 6 mM离子甘氨酸和6 mM碘乙酸)增强了非选择性阳离子通道活性，增加了[Ca(2+)](i)，并引发了细胞膜混乱，呋塞米(10 - 100µM)显著减弱了这一作用。暴露于叔丁基过氧化氢(0.1 -1 mM)的氧化应激同样增强了非选择性阳离子通道的活性，增加了[Ca(2+)](i)并引发了细胞膜混乱，而呋塞米(10 - 100µM)再次显著减弱了这一作用。[5]
结论:本研究首次表明，应用于微摩尔浓度(10 - 100µM)的环状利尿剂速尿可抑制人红细胞的非选择性阳离子通道活性和红细胞凋亡。[5]

Deaf Mouse Model and Study Groups[3]
A deaf mouse model (C57BL/6 mouse, 4–6 weeks of age, weight of 15–25 g) was created by intraperitoneal injection of KM (1000 mg/kg) followed by furosemide (100 mg/kg) within 30 min. In Experiment 1, to assess the initial temporal change of hearing and the extent of hair cell damage in this deaf mouse model, total nine mice were divided into three groups: Day-1 (N = 3), Day-2 (N = 3) and Day-3 (N = 3). After injection of KM and furosemide on day 0, hearing loss and cochlear hair cell damage were evaluated on day 1, day 2 and day 3, respectively (Supplementary file S1).[3]
In Experiment 2, to test the rescue effect of GV1001, total 120 mice were divided into the following three treatment groups: GV1001 (N = 40), dexamethasone (N = 40) and saline (N = 40). GV1001 (10 mg/kg), dexamethasone (15 mg/kg), or saline was subcutaneously administered for three consecutive days after the injection of KM and furosemide. To compare the rescue effect of GV1001 on different time points, each group was divided into four subgroups according to the time points of GV1001, dexamethasone, and saline treatment: D0 group (days 0, 1 and 2), D1 group (days 1, 2 and 3), D3 group (days 3, 4 and 5), and D7 group (days 7, 8 and 9; Supplementary file S2).[3]

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A deaf mouse model was created by intraperitoneal injection of KM and furosemide. First, to test the early temporal change of hearing and extent of hair cell damage after KM and furosemide injection, hearing and outer hair cells (OHCs) morphology were evaluated on day 1, day 2 and day 3 after injection. In the second experiment, following KM and furosemide injection, GV1001, dexamethasone, or saline were given for three consecutive days at different time points: D0 group (days 0, 1, and 2), D1 group (days 1, 2, and 3), D3 group (days 3, 4, and 5) and D7 group (days 7, 8, and 9). The hearing thresholds were measured at 8, 16, and 32 kHz before ototoxic insult, and 7 days and 14 days after KM and furosemide injection. After 14 days, each turn of the cochlea was imaged to evaluate OHCs damage. GV1001-treated mice showed significantly less hearing loss and OHCs damage than the saline control group in the D0, D1 and D3 groups (p < 0.0167). However, there was no hearing restoration or intact hair cell in the D7 group. GV1001 protected against cochlear hair cell damage, and furthermore, delayed administration of GV1001 up to 3 days rescued hair cell damage and hearing loss in KM/furosemide-induced deaf mouse model.[3]

Absorption, Distribution and Excretion
Following oral administration, furosemide is absorbed from the gastrointestinal tract. It displays variable bioavailability from oral dosage forms, ranging from 10 to 90%. The oral bioavailability of furosemide from oral tablets or oral solution is about 64% and 60%, respectively, of that from an intravenous injection of the drug.
The kidneys are responsible for 85% of total furosemide total clearance, where about 43% of the drug undergoes renal excretion. Significantly more furosemide is excreted in urine following the I.V. injection than after the tablet or oral solution. Approximately 50% of the furosemide load is excreted unchanged in urine, and the rest is metabolized into glucuronide in the kidney.
The volume of distribution following intravenous administration of 40 mg furosemide were 0.181 L/kg in healthy subjects and 0.140 L/kg in patients with heart failure.
Following intravenous administration of 400 mg furosemide, the plasma clearance was 1.23 mL/kg/min in patients with heart failure and 2.34 mL/kg/min in healthy subjects, respectively.
Significantly more furosemide is excreted in urine following the IV injection than after the tablet or oral solution. There are no significant differences between the two oral formulations in the amount of unchanged drug excreted in urine.
After oral administration of furosemide to 18 pregnant women on the day of delivery, substantial concentrations of the drug were detected in umbilical cord vein plasma as well as in amniotic fluid. The ratio between the furosemide concentrations in maternal vein plasma and in umbilical cord plasma increased with time and approximated unity at 8 to 10 hr after administration of the drug. The plasma half-life of furosemide appeared to be longer in the mothers than in nonpregnant healthy volunteers. In one patient the plasma level of furosemide was constant during 5 hr of observation.
In one study in patients with normal renal function, approx 60% of a single 80 mg oral dose of furosemide was absorbed from the GI tract. When admin to fasting adults in this dosage, the drug appeared in the serum within 10 min, reached a peak concn of 2.3 ug/mL in 60-70 min, & was almost completely cleared from the serum in 4 hr. When the same dose was given after a meal, the serum concn of furosemide increased slowly to a peak of about 1 ug/ml after 2 hr & similar concns were present 4 hr after ingestion. However, a similar diuretic response occurred regardless of whether the drug was given with food or to fasting patients. In another study, the rate & extent of absorption varied considerably when 1 g of furosemide was given orally to uremic patients. An avg of 76% of a dose was absorbed, & peak plasma concns were achieved within 2-9 hr (avg 4.4 hr). Serum concns required to produce max diuresis are not known, & it has been reported that the magnitude of response does not correlate with either the peak or the mean serum concns.
The diuretic effect of orally administered furosemide is apparent within 30 minutes to 1 hr and is maximal in the first or second hour. The duration of action is usually 6-8 hr. The maximum hypotensive effect may not be apparent until several days after furosemide therapy is begun. After iv administration of furosemide, diuresis occurs within 5 min, reaches a maximum within 20-60 min, and persists for approximately 2 hr. After im administration, peak plasma concentrations are attained within 30 min; onset of diuresis occurs somewhat later than after iv administration. In patients with severely impaired renal function, the diuretic response may be prolonged.
For more Absorption, Distribution and Excretion (Complete) data for Furosemide (15 total), please visit the HSDB record page.

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Metabolism / Metabolites
The metabolism of furosemide occurs mainly in the kidneys and the liver, to a smaller extent. The kidneys are responsible for about 85% of total furosemide total clearance, where about 40% involves biotransformation. Two major metabolites of furosemide are furosemide glucuronide, which is pharmacologically active, and saluamine (CSA) or 4-chloro-5-sulfamoylanthranilic acid.
It would appear that frusemide glucuronide is the only or at least the major biotransformation metabolite in man. 2-amino-4- chloro-5-sulfamoylanthranilic acid has been reported in some studies but not in others; and is thought to be an analytical artifact.
In patients with normal renal function, a small amount of furosemide is metabolized in the liver to the defurfurylated derivative, 4-chloro-5-sulfamoylanthranilic acid. ...

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Biological Half-Life
The half-life from the dose of 40 mg furosemide was 4 hours following oral administration and 4.5 hours following intravenous administration. The terminal half-life of furosemide is approximately 2 hours following parenteral administration. The terminal half-life may be increased up to 24 hours in patients with severe renal failure.
To study the pharmacokinetics of furosemide (fursemide; Lasix) and its acyl glucuronide and to analyze the pharmacodynamic response, a study was conducted in 7 healthy subjects, mean age 34 yr, who received a single oral 80 mg dose of furosemide in tablet form. Two half-lives were distinguished in the plasma elimination of furosemide and its conjugate, with values of 1.25 and 30.4 hr for furosemide and 1.31 and 33.2 hr for the conjugate. ...
In dogs, ... the elimination half life /is/ approximately 1-1.5 hours.
Various investigators have reported a wide range of elimination half-lives for furosemide. In one study, the elimination half-life averaged about 30 minutes in healthy patients who received 20-120 mg of the drug IV. In another study, the elimination half-life averaged 9.7 hours in patients with advanced renal failure who received 1 g of furosemide IV. The elimination half-life was more prolonged in 1 patient with concomitant liver disease.
The serum half-life in therapeutic doses is 92 minutes; increasing in patients with uremia; congestive heart failure and cirrhosis as well as in the neonate and aged patients. In such patients the half-life may be extended to 20 hours.

Toxicity Summary
IDENTIFICATION AND USE: Furosemide is white or slightly yellow, solid powder or crystals. Furosemide is used to treat edema associated with many diseases (either as the sole drug or as an adjunct to other antihypertensives). HUMAN STUDIES: Overdoses of diuretics are uncommon and infrequently serious. Problems most frequently involve chronic over medication or poor monitoring and/or lack of anticipation of drug interactions or not compensating for concomitant hepatic or renal dysfunction. Main toxic effects are on the kidneys with diuresis of water, sodium, and potassium leading most frequently to a hyponatremic, hypokalemic, and hypochloremic dehydration. More caution is warranted with patients at higher risk for abnormal renal function including patients with any renal disease, diabetes mellitis, and borderline fluid and/or electrolyte status. In a hospital-based study of adverse reactions to medications there was a 21% rate of adverse affects to frusemide with most common ones being hypovolemia, hyperuricemia, and hypokalemia which for the most part were mild, but the rate and severity increased with increasing daily doses. Hypersensitivity reactions such as rash, photosensitivity, thrombocytopenia, and pancreatitis are rare. Life threatening hyperkalemia and reversible renal failure occurred in an elderly male taking captopril concomitantly with furosemide. Acute rhabdomyolysis and myoglobinuria due to hypokalaemia occurred in a 74-year-old male taking furosemide. Severe anaphylactic reaction to furosemide involving urticaria; angioedema and hypotension occurred in an adult 5 minutes after receiving intravenous furosemide. Furosemide abuse (400 mg daily) was associated with severe hyponatremia and central pontine myelinolysis. Self-administration of furosemide over 6 years resulted in calcification of the renal medulla. Nephrocalcinosis and nephrolithiasis occurred in 5 children after treatment with furosemide. It has also reported nephrocalcinosis in premature infants being treated with furosemide. Cholelithiasis in infants was caused by furosemide. Tachycardia was reported following a high dose intravenous regimen using furosemide. Renal calcifications were encountered in premature infants when given furosemide. Furosemide-induced renal calcifications in low birth weight infants may lead to glomerular and tubular dysfunction in the long-term. A concentration-dependent increase in the frequency of chromosomal aberrations was observed in human lymphocytes exposed in vitro to furosemide for 24 and 72 hr. No such effect was detected in the human fibroblast cell line. ANIMAL STUDIES: Chronic administration to rats has caused tubular degeneration in the kidneys. Calcification and damage to the renal parenchyma occurred in a subchronic study in dogs. Developmental studies have been conducted in mice, rats and rabbits. An increase in the incidence and severity of hydronephrosis (distention of the renal pelvis and occasionally the ureters) was seen in a mouse study and one of three rabbit studies. In male mice treated intraperitoneally with furosemide at 0.3-50 mg/kg bw, a non-dose-dependent increase in the percentage of meiotic cells with chromosomal aberrations was observed during the whole spermatogenic cycle. Furosemide was tested over a wide range of doses (0, 100, 333, 1000, 3333, and 10,000 ug/plate) in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) with and without metabolic activation. Furosemide was negative in these tests and the highest ineffective dose level tested in any Salmonella tester strain was 10,000 ug/plate. Furosemide was reported to induce mutations in L5178Y mouse lymphoma cells in the presence of an exogenous metabolic system only at the highest concentration tested (1500 ug/mL). It was also reported to induce sister chromatid exchange and chromosomal aberrations in Chinese hamster CHO cells at 3750 and 500 ug/mL in the presence and absence of an exogenous metabolic system. Furosemide induced chromosomal damage in Chinese hamster lung fibroblasts in vitro, but only in the absence of an exogenous metabolic system. ECOTOXICITY STUDIES: Furosemide in combination with other drugs found in waste water was genotoxic to zebrafish, and exhibited toxic effects on riverine microbial communities.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because little information is available on the use of furosemide during breastfeeding and because intense diuresis from high doses might decrease lactation, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Low doses of furosemide (20 mg daily) do not suppress lactation.
◉ Effects in Breastfed Infants
Anecdotal, short-term observations at one medical center found no adverse infant effects from maternal use of furosemide in the immediate postpartum period.
◉ Effects on Lactation and Breastmilk
Furosemide 20 mg intramuscularly on the first postpartum day followed by 40 mg orally for 4 days has been used in conjunction with fluid restriction and breast binding to suppress lactation within 3 days postpartum. The added contribution of furosemide to fluid restriction and breast binding, which are effective in suppressing lactation, is not known. No data exist on the effects of loop diuretics on established lactation.
A randomized, controlled trial compared postpartum furosemide (n = 192) to placebo (n = 192) in women who had gestational hypertension and preeclampsia. Patients received either a 4- to 5-day course of 20 mg oral furosemide daily or placebo. The first dose was given 6 to 24 hours postpartum and then every 24 hours thereafter until hospital discharge. No difference was found in patient-reported breastfeeding difficulties between the two groups.
A study of mothers with antepartum hypertension were given either furosemide 20 mg or a placebo daily for 5 days postpartum. Mothers reported whether they were exclusively breastfeeding at 2 and 6 weeks postpartum. No difference was found in the rates of exclusive breastfeeding between the furosemide and placebo groups.

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Protein Binding
Plasma concentrations ranging from 1 to 400 mcg/mL are about 91-99% bound in healthy individuals. The unbound fraction is about 2.3-4.1% at therapeutic concentrations. Furosemide mainly binds to serum albumin.

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Interactions
Methotrexate and other drugs that, like Lasix, undergo significant renal tubular secretion may reduce the effect of Lasix. Conversely, Lasix may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both Lasix and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of Lasix.
Phenytoin interferes directly with renal action of Lasix. There is evidence that treatment with phenytoin leads to decreased intestinal absorption of Lasix, and consequently to lower peak serum furosemide concentrations.
Lasix may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively.
There is a risk of ototoxic effects if cisplatin and Lasix are given concomitantly. In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if Lasix is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.
For more Interactions (Complete) data for Furosemide (36 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat (female) oral 2600 mg/kg
LD50 Rat (male) oral 2820 mg/kg
LD50 Rat ip 800 mg/kg
LD50 Rat iv 800 mg/kg
For more Non-Human Toxicity Values (Complete) data for Furosemide (11 total), please visit the HSDB record page.

[1]. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. J Biol Chem. 1996 Jul 5;271(27):16237-44.

[2]. Residues in transmembrane domains I and II determine gamma-aminobutyric acid type AA receptor subtype-selective antagonism by Furosemide sodium. Mol Pharmacol. 1999 Jun;55(6):993-9.

[3]. Novel Peptide Vaccine GV1001 Rescues Hearing in Kanamycin/Furosemide sodium-Treated Mice. Front Cell Neurosci. 2018 Jan 19;12:3.

[4]. Furosemide sodium, a blocker of Na+/K+/2Cl- cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state. J Physiol Sci. 2006 Dec;56(6):401-6.

[5]. Inhibitory effect of Furosemide sodium on non-selective voltage-independent cation channels in human erythrocytes.Cell Physiol Biochem. 2012;30(4):863-75.

Therapeutic Uses
Diuretics; Sodium Potassium Chloride Symporter Inhibitors
Oral Lasix may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Hypertensive patients who cannot be adequately controlled with thiazides will probably also not be adequately controlled with Lasix alone. /Included in US product labeling/
Lasix is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Lasix is particularly useful when an agent with greater diuretic potential is desired. /Included in US product labeling/
IV furosemide has been found useful as an adjunct to hypotensive agents in the treatment of hypertensive crises, especially when associated with acute pulmonary edema or renal failure. In addition to producing a rapid diuresis, furosemide enhances the effects of other hypotensive drugs and counteracts the sodium retention caused by some of these agents. /NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for Furosemide (11 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ Lasix (furosemide) is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dose schedule must be adjusted to the individual patient's needs.
Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. As with any effective diuretic, electrolyte depletion may occur during Lasix therapy, especially in patients receiving higher doses and a restricted salt intake. Hypokalemia may develop with Lasix, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives. Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects.
Patients receiving furosemide must be carefully observed for signs of hypovolemia, hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and hypomagnesemia. Patients should be informed of the signs and symptoms of electrolyte imbalance and instructed to report to their physicians if weakness, dizziness, fatigue, faintness, mental confusion, lassitude, muscle cramps, headache, paresthesia, thirst, anorexia, nausea, and/or vomiting occur. Excessive fluid and electrolyte loss may be minimized by initiating therapy with small doses, careful dosage adjustment, using an intermittent dosage schedule if possible, and monitoring the patient's weight. To prevent hyponatremia and hypochloremia, intake of sodium may be liberalized in most patients; however, patients with cirrhosis usually require at least moderate sodium restriction while on diuretic therapy. Determinations of serum electrolytes, BUN, and carbon dioxide should be performed early in therapy with furosemide and periodically thereafter. If excessive diuresis and/or electrolyte abnormalities occur, the drug should be withdrawn or dosage reduced until homeostasis is restored. Electrolyte abnormalities should be corrected by appropriate measures.
Furosemide should be used with caution in patients with hepatic cirrhosis because rapid alterations in fluid and electrolyte balance may precipitate hepatic precoma or coma.
For more Drug Warnings (Complete) data for Furosemide (29 total), please visit the HSDB record page.

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Pharmacodynamics
Furosemide manages hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide is a potent loop diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption from the proximal and distal tubules, as well as the loop of Henle. It works directly acts on the cells of the nephron and indirectly modifies the content of the renal filtrate. Ultimately, furosemide increases the urine output by the kidney. Protein-bound furosemide is delivered to its site of action in the kidneys and secreted via active secretion by nonspecific organic transporters expressed at the luminal site of action. Following oral administration, the onset of the diuretic effect is about 1 and 1.5 hours, and the peak effect is reached within the first 2 hours. The duration of effect following oral administration is about 4-6 hours but may last up to 8 hours. Following intravenous administration, the onset of effect is within 5 minutes, and the peak effect is reached within 30 minutes. The duration of action following intravenous administration is approximately 2 hours. Following intramuscular administration, the onset of action is somewhat delayed.

C12H11CLN2O5S

330.74

330.007

C, 43.58; H, 3.35; Cl, 10.72; N, 8.47; O, 24.19; S, 9.69

54-31-9

Furosemide sodium;41733-55-5;Furosemide-d5;1189482-35-6;42461-27-8 (HCl); 54-31-9; 41733-55-5 (sodium); 61422-49-9 (xantinol)

3440

White to light yellow crystalline powder.

1.6±0.1 g/cm3

582.1±60.0 °C at 760 mmHg

220 °C (dec.)(lit.)

305.9±32.9 °C

0.0±1.7 mmHg at 25°C

1.658

3.1

131.01

3

7

5

21

481

0

ClC1C([H])=C(C(C(=O)O[H])=C([H])C=1S(N([H])[H])(=O)=O)N([H])C([H])([H])C1=C([H])C([H])=C([H])O1

ZZUFCTLCJUWOSV-UHFFFAOYSA-N

InChI=1S/C12H11ClN2O5S/c13-9-5-10(15-6-7-2-1-3-20-7)8(12(16)17)4-11(9)21(14,18)19/h1-5,15H,6H2,(H,16,17)(H2,14,18,19)

4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoic acid

Lasix; Frusemide; Lasix; Furanthril; Furosemid; Errolon; Fusid; Furosemide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~302.35 mM)
H2O : ~0.1 mg/mL (~0.30 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.56 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (7.56 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。