Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FUROSEMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed2001

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure.

PURPOSE: Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide. PATIENTS AND METHODS: We conducted an open-label trial of 234 patients with chronic heart failure (mean [+/- SD] age, 64 +/- 11 years) from an urban public health care system. Patients received oral torsemide (n = 113) or furosemide (n = 121) for 1 year. The primary endpoint was readmission to the hospital for heart failure. Secondary endpoints included readmission for all cardiovascular causes and for all causes, numbers of hospital days, and health-related quality of life. RESULTS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to need readmission for heart failure (39 [32%] vs. 19 [17%], P <0.01) or for all cardiovascular causes (71 [59%] vs. 50 [44%], P = 0.03). There was no difference in the rate of admissions for all causes (92 [76%] vs. 80 [71%], P = 0.36). Patients treated with torsemide had significantly fewer hospital days for heart failure (106 vs. 296 days, P = 0.02). Improvements in dyspnea and fatigue scores from baseline were greater among patients treated with torsemide, but the differences were statistically significant only for fatigue scores at months 2, 8, and 12. CONCLUSIONS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued. If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for patients with chronic heart failure.

Aged↗
PubMed1997

Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations.

BACKGROUND: Use of intravenous furosemide is generally avoided in critically ill neonates and infants soon after open heart operations to prevent fluctuations in intravascular volume and resulting circulatory instability. METHODS: To assess and compare the safety and efficacy of continuous versus intermittent intravenous furosemide, we undertook a prospective, randomized trial in 26 consecutive patients less than 6 months of age. Inclusion criteria were presence of low-output syndrome requiring inotropic support (24/26 patients) or pulmonary hypertension requiring vasodilator therapy (10/26 patients) within 6 hours of discontinuation of cardiopulmonary bypass. Eleven patients received 0.1 mg x kg(-1) x h(-1) continuous intravenous furosemide (group 1) and 15 received 1 mg/kg bolus every 4 hours (group 2) for 24 hours. Mean age (3.7 +/- 3.4 versus 1.8 +/- 2.5 months) and weight (4.6 +/- 2.1 versus 4.3 +/- 1.7 kg) were comparable. RESULTS: Group 2 infants showed slightly greater absolute urinary output (2.5 +/- 1.1 mL/kg per hour versus 3.3 +/- 1.1 mL/kg per hour, p = 0.05). However, urinary output per dose of drug was significantly larger in group 1 infants (1.0 +/- 0.4 versus 0.5 +/- 0.2 mL x kg(-1) x h(-1); p = 0.002) with lesser fluctuations (variance, 1.9 +/- 1.6 versus 3.8 +/- 2.1; p = 0.02) and fluid replacement needs (20.6 +/- 3.8 versus 51.8 +/- 14.4; p = 0.001). Electrolyte replacement requirements were similar. A trend toward greater hemodynamic instability in group 2 patients (heart rate variance 88.4 +/- 79.8 versus 128.3 +/- 82.7; p = 0.09; central venous pressure variance 2.8 +/- 1.90 versus 4.1 +/- 3.7; p = 0.07; mixed venous oxygen saturation variance, 32.3 +/- 27.6 versus 45.7 +/- 20.4; p = 0.06) was noted. All patients who completed the study protocol survived operation and were discharged home. CONCLUSIONS: We conclude that (1) commonly used doses of both intermittent and continuous intravenous furosemide infusion can be safely administered to critically ill neonates and infants as early as 6 hours after operation, (2) continuous infusion yields an almost comparable urinary output with a much lower dose of furosemide, and (3) intermittent administration is associated with greater fluctuations in urinary output and greater needs for fluid replacement therapy.

Cardiac Output, Low↗
PubMed1996

Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration.

OBJECTIVE: Physiologic indirect-response models have been proposed to account for the pharmacodynamics of drugs with an indirect mechanism of action, such as furosemide. However, they have not been applied to tolerance development. The aim of this study was to investigate the development of tolerance after multiple intravenous dosing of furosemide in healthy volunteers. METHODS: Three repetitive doses of 30 mg furosemide were given as rapid intravenous infusions at 0, 4, and 8 hours to eight healthy volunteers. Urine samples were collected for a period up to 14 hours after the first dose. Volume and sodium losses were isovolumetrically replaced with an oral rehydration fluid. RESULTS: Tolerance was demonstrated as a significant decrease in diuretic and natriuretic response over time. Total mean diuresis was 35% lower (p < 0.01) and total mean natriuresis was 52% lower (p < 0.0001) after the third dose of furosemide compared with the first dose. However, there were considerable interindividual variations in the rate and extent of tolerance development for both diuresis and natriuresis. Pharmacokinetic-pharmacodynamic modeling of tolerance development was performed with use of an indirect-response model with an additional "modifier" compartment. This model gave an accurate description of the diuretic and natriuretic data after multiple dosing of furosemide and enabled the estimation of a lag-time for tolerance and a rate constant for tolerance development. Physiologic counteraction was demonstrated as a significant increase in plasma active renin levels (p < 0.00001) and a decrease in atrial natriuretic peptide levels (p < 0.005) during the day, concomitantly with the development of a negative sodium balance. This may be viewed as physiologic reflections of the modifier in our model. CONCLUSION: Indirect-response models may be successfully applied for tolerance modeling of drugs after multiple dosing.

Adult↗
PubMed1998

The main determinant of furosemide inhibition on GABA(A) receptors is located close to the first transmembrane domain.

Inhibitory GABA(A) receptors are regulated by numerous allosteric modulators, the most receptor-subtype specific of which is furosemide. It recognises receptors of the subunit composition alpha6beta2/3gamma2, restricted to cerebellar granule cells. To locate furosemide's site of action we constructed chimeras of the furosemide-sensitive alpha6 and the furosemide-insensitive alpha1 subunit, and expressed and studied them together with the beta3 and gamma2 subunits in Xenopus oocytes by the two-electrode voltage clamp technique. The inhibition of GABA-induced currents by furosemide mainly depended on a short domain proximal to the first transmembrane region of the alpha6 subunit.

Allosteric Regulation↗
PubMed1984

Quantitative determination of furosemide in plasma, plasma water, urine and ascites fluid by high-performance liquid chromatography.

A high-performance liquid chromatographic method using spectrofluorometric detection is described for the determination of furosemide in plasma, plasma water, urine and ascites fluid. The extraction procedure decreases interference from endogenous substances. The detection limit of furosemide is 10 ng in 0.5 ml of biological sample. The method is sufficiently sensitive for pharmacokinetic study of furosemide with normal subjects and patients with liver cirrhosis and/or renal disease after oral administration of furosemide in a retard capsule, and for study of protein binding of furosemide in patients with various diseases.

Ascitic Fluid↗
PubMed1990

Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia.

To test the hypothesis that alternate-day administration of furosemide will result in a sustained improvement in pulmonary function without causing alterations in electrolyte or mineral homeostasis, we conducted a randomized, double-blind, placebo-controlled study of 11 hospitalized, oxygen-dependent, spontaneously breathing infants with chronic bronchopulmonary dysplasia. Infants were randomly selected to receive either furosemide, 4 mg/kg in two divided doses on alternate days orally, or placebo for 8 days, followed by crossover to the alternate-therapy for an additional 8-day period. The two study periods were separated by a 48-hour washout period. Dynamic compliance, total pulmonary resistance, the concentration of electrolytes in serum, and the concentrations of calcium and creatinine in urine were measured on nontreatment days. Alternate-day furosemide therapy increased dynamic lung compliance by 76 +/- 112% and decreased total pulmonary resistance by 20 +/- 39%, compared with placebo (both variables p = 0.032). Alternate-day furosemide therapy did not result in increased urine output, electrolyte abnormalities, or increased urinary calcium excretion. We conclude that this simplified treatment regimen may be useful in the management of infants with chronic bronchopulmonary dysplasia. The results support our previous speculation that furosemide improves pulmonary function by mechanisms unrelated to its diuretic properties.

Airway Resistance↗
PubMed1992

Kidney function in very low birth weight infants with furosemide-related renal calcifications at ages 1 to 2 years.

To determine whether long-term renal sequelae follow the use of furosemide in preterm infants, we evaluated renal function in 27 former very low birth weight infants (less than 1500 gm) at 1 to 2 years of age. Patients were classified into three groups on the basis of status at the time of discharge from the hospital: group 1 (n = 7) had no furosemide treatment or renal calcifications, group 2 (n = 10) had furosemide therapy but no calcifications, and group 3 (n = 10) had furosemide therapy with renal calcifications. Renal ultrasonography at the time of the study demonstrated resolution of the calcifications in six patients in group 3. No differences in renal function were observed between groups 1 and 2. Creatinine clearance (mean +/- SEM) in group 3 (83.6 +/- 7.8 ml/min per 1.73 m2) was significantly lower than clearance in groups 1 and 2 (103.2 +/- 6.5 and 109.1 +/- 5.1, respectively; p less than 0.05). Children in group 3 had significantly higher urinary calcium/creatinine ratios and fractional excretion of sodium and lower tubular reabsorption of phosphate than children in the two other groups had. Urine-blood difference in carbon dioxide tension after oral acetazolamide load, which indicates the ability of the distal tubule to secrete hydrogen ions, was 8.4 +/- 3.4 mm Hg in group 3, significantly lower than values in groups 1 and 2 (22.6 +/- 3.1 and 28.0 +/- 4.3 mm Hg, respectively, p less than 0.05). Within group 3 the four children with persistent renal calcifications had significantly lower urine-blood carbon dioxide tension differences than did those with resolution of calcifications (p = 0.02). We conclude that furosemide-related renal calcifications in very low birth weight infants may lead to glomerular and tubular dysfunction; further long-term follow-up of this population is recommended.

Absorption↗
PubMed1978

The pharmacologic effects of furosemide therapy in the low-birth-weight infant.

The pharmacologic effects of furosemide were studied in six infants (mean gestation 30.7 weeks; mean birth weight 1,490 gm) at ages 10 to 57 days. Furosemide (for clinical indication, standardized at 1 mg/kg) was given intravenously over one minute; data were collected over the ensuing 24 hours. For three hours following furosemide administration, a significant diuresis was observed. Sodium excretion, percent fractional sodium excretion, and potassium excretion were significantly increased and urinary pH significantly decreased for six hours following the administration of furosemide. Creatinine and free water clearances were slightly elevated, although not significantly. Furosemide is an effective diuretic, the onset of pharmacologic action was within one hour, the peak action was sustained for three hours, and the duration of action was six hours. The net fluid, sodium, and potassium losses following a 1 mg/kg single dose were 28 ml, and 3.6 and 0.3 mEq/kg, respectively.

Furosemide↗
PubMed1978

Urinary excretion of prostaglandin E following the administration of furosemide and indomethacin to sick low-birth-weight infants.

Urinary excretion of prostaglandin E was measured in seven sick low-birth-weight infants. Four had severe hyaline membrane disease and one had chronic bronchopulmonary dysplasia; all received furosemide. Two infants had patent ductus arteriosus and received indomethacin. Following administration of furosemide, urine volume and the excretion rates of sodium and calcium were significantly increased; such changes were not seen following the administration of indomethacin. Prostaglandin E excretion rate was increased from 0.4 +/- 0.04 to 1.3 +/- 0.2 ng/mg Cr (mean +/- SEM) following administration of furosemide, but decreased in two patients following administration of indomethacin. The present results demonstrate that furosemide enhances urinary excretion of prostaglandin E by mechanisms which may reflect an increase in prostaglandin synthesis, a decrease in prostaglandin renal metabolism, or both. Indomethacin, which is a prostaglandin synthetase inhibitor, decreases the urinary excretion of prostaglandin E. These observations suggest that furosemide therapy in patients receiving indomethacin may be ineffective.

Calcium↗
PubMed1985

Controlled trial of furosemide therapy in infants with chronic lung disease.

To study the effects of furosemide therapy in infants with chronic lung disease (CLD), a double-blind controlled trial was designed. Seventeen infants with evidence of CLD (oxygen requirements greater than 30% at greater than 3 weeks of age and chest radiographic findings consistent with CLD) were studied. Pulmonary function was measured immediately before, and after 48 hours and 7 days of treatment with furosemide (1 mg/kg/12 hr intravenously or 2 mg/kg/12 hr orally) or placebo. Clinical status improved in six of seven infants who received furosemide and in two of 10 infants who received placebo (P less than 0.002). In the furosemide group, ventilator and oxygen requirements decreased (P less than 0.003); minute ventilation, alveolar ventilation, and dynamic compliance increased; and venous admixture decreased (P less than 0.05). There were no significant changes in the placebo group. Our findings suggest that furosemide significantly improves lung function during therapy in infants with CLD and allows earlier weaning from ventilatory support and supplemental oxygen.

Chronic Disease↗
PubMed1996

Impaired response to furosemide in hyperprostaglandin E syndrome: evidence for a tubular defect in the loop of Henle.

In hyperprostaglandin E syndrome (HPS) renal wasting of electrolytes and water is consistently associated with enhanced synthesis of prostaglandin E2. In contrast to Bartter or Gitelman syndrome (BS/GS), HPS is characterized by its severe prenatal manifestation, leading to fetal polyuria, development of polyhydramnios, and premature birth. This disorder mimics furosemide treatment with hypokalemic alkalosis, hypochloremia, isosthenuria, and impaired renal conservation of both calcium and magnesium. Therefore the thick ascending limb of the loop of Henle seems to be involved in HPS. To characterize the tubular defect we investigated the response to furosemide (2 mg/kg) in HPS (n = 8) and BS/GS (n = 3) 1 week after discontinuation of long-term indomethacin treatment. Sensitivity to furosemide was completely maintained in patients with BS/GS. The diuretic, saluretic, and hormonal responses were similar to those of a control group of healthy children (n = 13), indicating an intact function of the thick ascending limb of the loop of Henle in BS/GS. In contrast, patients with HPS had a marked resistance to this loop diuretic. Furosemide treatment increased urine output by 7.5 +/- 0.7 ml/kg per hour in healthy control subjects but only by 4.4 +/- 1.2 ml/kg per hour (p < 0.5) in children with HPS. In parallel, the latter also had a markedly impaired saluretic response (delta Cl(urine) 0.14 +/- 0.04 mmol/kg per hour vs 0.85 +/- 0.09 mmol/kg per hour, p < 0.001; delta Na(urine) 0.23 +/- 0.06 mmol/kg per hour vs 0.77 +/- 0.09 mmol/kg per hour, p < 0.001). Furosemide therapy further enhanced prostaglandin E2 excretion in patients with HPS (54 +/- 17 to 107 +/- 28 ng/hr per 1.73 m2, p < 0.05), whereas no significant effect was observed in healthy children (20 +/- 3 to 12 +/- 3 ng/hr per 1.73 m2). We conclude that a defect of electrolyte reabsorption in the thick ascending limb of the loop of Henle plays a major role in HPS.

Bartter Syndrome↗
PubMed1993

The effect of furosemide-induced diuresis on rabbit micturition and bladder contractile function.

The morphology and contractile function of the urinary bladder can be significantly altered in response to specific forms of physiological and pathophysiological stress placed upon it. For example, partial outlet obstruction results in a marked increase in bladder mass (weight) with associated alterations in the contractile response to specific forms of stimulation. Diabetes and its associated diuresis also induce significant alterations in bladder weight and contractile function. The current study was designed to determine if the increase in bladder weight induced by diuresis is associated with contractile alterations similar to those observed following partial outlet obstruction. Diuresis was induced by continual slow-infusion of furosemide using osmotic pumps. The results can be summarized as follows: 1) After two weeks of furosemide treatment the bladder mass was significantly greater than in the controls. 2) Furosemide-treated rabbits consumed and excreted three times more fluid than did the controls. 3) In vivo cystometric capacity and bladder compliance of the furosemide-treated rabbits were significantly increased. 4) Diuresis induced a significant increase in the contractile response of isolated bladder body strips to field stimulation, ATP, bethanechol, and KCl. 5) Furosemide treatment had no effects on the contractile responses of bladder base strips to any form of stimulation. Diuresis resulted in a significant increase in bladder weight and an associated increase in the contractile state of the bladder body, presumably through an increase in smooth muscle.

Adenosine Triphosphate↗
PubMed1985

Effect of furosemide on dialysis requirement following cadaveric kidney transplantation.

High doses of furosemide have been reported to reduce the requirement for dialysis following cadaveric kidney transplantation. Depending on recipient age, alternate cadaver kidney transplant recipients received infusions of 200 to 400 mg. furosemide just before restoration of renal circulation. All recipients received infusions of mannitol during the hour before renal revascularization. All 50 kidneys were preserved with intracellular electrolyte solutions. Mean cold storage times (33.4 plus or minus 11.4 hours for recipients given furosemide versus 35.7 plus or minus 12.3 hours for controls) were not significantly different between the 2 groups. There were no significant differences in first week dialysis requirement between recipients given furosemide and controls (75 versus 73 per cent, respectively), first day urine output (2.2 plus or minus 4.2 versus 1.0 plus or minus 0.81., respectively), 1-month serum creatinine nadirs (2.1 plus or minus 1.1 versus 1.9 plus or minus 1.1 mg . per dl., respectively) and 1-month function rate (92 versus 92 per cent, respectively). High doses of furosemide did not prevent significant acute tubular necrosis following human cadaveric kidney transplantation when the recipients also received infusions of mannitol.

Adult↗
PubMed2002

Furosemide reveals heterogeneous GABA(A) receptor expression at adult rat Golgi cell to granule cell synapses.

The contribution that alpha6 subunit-containing GABA(A) receptors make to inhibitory synaptic transmission to granule cells was investigated by making whole-cell patch clamp recordings from granule cells in adult rat cerebellar slices and applying furosemide, the specific alpha6 subunit-containing GABA(A) receptor antagonist. Endogenous, extracellular GABA continually activated GABA(A) receptors producing a tonic current. Since this current was markedly reduced by furosemide it was probably produced by alpha6 subunit-containing receptors. In contrast, furosemide had little effect on the amplitude or kinetics of fast spontaneous inhibitory postsynaptic currents (sIPSCs), although such sIPSCs were abolished by bicuculline and SR95331. However, the amplitude of evoked IPSCs with a very slow rise and decay were markedly reduced by furosemide. These IPSCs probably resulted from the spillover of GABA from neighbouring synapses activating high affinity alpha6 subunit-containing receptors. In the rest of the cells (40 out of 46), evoked IPSCs had rise and decay kinetics that lay in-between fast sIPSCs and slow 'spillover' IPSCs. Such IPSCs had variable kinetics and also exhibited considerable variation in the magnitude of furosemide block. Thus the GABA(A) receptors present at adult Golgi cell-granule cell synapses, at a developmental stage where receptor expression is complete, are highly heterogeneous.

Animals↗
PubMedDate not supplied

Plasma pharmacokinetics of intravenous and intramuscular furosemide in the camel (Camelus dromedarius).

Single bolus intravenous (i.v.) and intramuscular (i.m.) doses of furosemide (1.5 mg kg(-1)) were administered in a crossover design to three female and three male adult, dromedary camels. Plasma furosemide concentrations were assayed by HPLC and sodium, potassium and chloride concentrations were measured using ion-selective electrodes. Plasma furosemide concentration-time plots indicated multi-compartment disposition, and there was considerable intersubject variability in the pharmacokinetic parameters. The mean (SD) i.v. terminal elimination half-life was 118 (67) minutes. The systemic clearance was 5.4 (1.2) ml min(-1) kg(-1). and the steady-state volume of distribution was 0.43 (0.14) litre kg(-1). The mean absorption time after i.m. dosing was 33 (62) minutes, while the absolute bioavailability was 71 (20) per cent. The glucuronide metabolite of furosemide was not detected in plasma. Clearance was lower, volume of distribution was larger, and half-life was longer compared with published data for dogs, horses, rats and humans. Plasma potassium and sodium concentrations were significantly diminished (P<0.05) by an average of 35.6 per cent (two to six hours post-dose) and 11.3 per cent (eight hours post-dose), respectively. Plasma chloride concentrations were not significantly affected by furosemide administration.

Animals↗
PubMed2003

Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety.

BACKGROUND/AIMS: The most rational treatment of moderate ascites is spironolactone alone or in combination with furosemide. However, it is unknown which of these two treatment schedules is preferable. METHODS: One hundred nonazotemic cirrhotic patients with moderate ascites were randomly assigned to be treated with spironolactone and furosemide (Group 1: 50 patients) or with spironolactone alone (Group 2: 50 patients). If no response was obtained, the doses of diuretics were increased up to 400 mg/day of spironolactone and 160 mg/day of furosemide. In patients of group 2 not responding to 400 mg/day of spironolactone, furosemide was added. In cases with an excessive response, the dosage of diuretics was reduced. RESULTS: The response rate (98% in Group 1 vs. 94% in Group 2), the rapidity of ascites mobilization and the incidence of complications induced by diuretic therapy was similar in both groups. The need to reduce the diuretic dosage was significantly higher in Group 1 than Group 2 (68% vs. 34%; P=0.002). CONCLUSIONS: In the treatment of moderate ascites, spironolactone alone seems to be as safe and effective as spironolactone associated with furosemide. Since spironolactone alone requires less dose adjustment, it would be more suitable for treating ascites on an outpatient basis.

Aged↗
PubMed1993

Advantages of the new loop diuretic torasemide over furosemide in patients with cirrhosis and ascites. A randomized, double blind cross-over trial.

Torasemide is a new loop diuretic with a longer half-life and longer action than furosemide in healthy subjects. In order to evaluate the pharmacodynamic effects, single oral doses of furosemide (80 mg) and torasemide (20 mg), which were equipotent in healthy subjects, were given to 14 patients with cirrhosis and ascites. Before the study patients underwent an equilibration period of 4 days without diuretics. The drugs were alternated following a randomized double-blind cross-over design after a wash-out period of at least 2 days. Urine was collected at defined intervals for 24 h after drug administration and blood samples were taken before, 6 h and 24 h after medication. Torasemide induced greater cumulative 24 h diuresis (2863 +/- 343 vs. 2111 +/- 184 ml, p < 0.01) than furosemide. Torasemide did not differ from furosemide for cumulative 0-6 h sodium excretion (96 +/- 17 vs. 92 +/- 23 mmol sodium) but caused a more pronounced cumulative 6-24 h natriuresis (38 +/- 11 vs. 17 +/- 4 mmol, p < 0.05). Five patients exhibited a weak response to furosemide (0-36 mmol sodium/24 h, median 24 mmol; 690-1460 ml urinary volume/24 h, median 1325 ml). These patients showed significantly higher natriuresis and diuresis following torasemide (26-136 mmol sodium/24 h, median 78 mmol, p < 0.05; 1670-3610 ml urinary volume/24 h, median 2200 ml, p < 0.05). Twenty-four hours after administration of both drugs there were no significant changes in hemodynamic, renal or hormonal parameters. No adverse effects were noted with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Bimodal action of furosemide on convulsant [3H]EBOB binding to cerebellar and cortical GABA(A) receptors.

Picrotoxinin-sensitive binding of a convulsant 4'-ethynyl-4-n[2,3-3H2]propyl-bicycloorthobenzoate ([3H]EBOB) to gamma-aminobutyric acid type A (GABA(A)) receptors was characterized in rat cerebrocortical and cerebellar membranes. The non-penetrating organic anions, furosemide and niflumate, in spite of their structural similarities, exerted differential effects on [3H]EBOB binding. Furosemide, a loop diuretic and a specific antagonist of a cerebellar GABA(A) receptor population, and GABA decreased the inhibitory potencies of each other in the cerebellum, while enhanced them in the cortex. The inhibitory potencies of niflumate, an anti-inflammatory and a chloride channel blocker. and GABA were enhanced by each other both in the cerebellum and cortex. Removal of chloride ions did not modify the effects of furosemide on [3H]EBOB binding. Furosemide antagonized the inhibition of cerebellar [3H]EBOB binding by a low pentobarbital concentration (0.1 mM), but enhanced the inhibition by a high concentration (0.5 mM). The results indicate that [3H]EBOB binding can be used to detect the known pharmacological features of the cerebellar granule cell-specific 16 subunit-containing GABA(A) receptors. The data extends the properties of furosemide antagonism of this receptor subtype to chloride insensitivity and interactions with barbiturate sites.

Animals↗