Metabolic effects of long-term therapy with muzolimine and chlorthalidone in hypertension. Previous short-term studies of muzolimine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthalidone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentrations remained unchanged, while a significant fall in potassium occurred with chlorthalidone. Neither drug affected the activity of sodium-potassium cotransport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial
Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide. Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. This is a potential advantage in the treatment of ascites in advanced cirrhosis since these patients have a low tolerance to sudden reductions of blood volume. Equivalent single, oral doses of furosemide (40 mg) and muzolimine (30 mg) were given to 10 cirrhotic patients with ascites and reduced renal perfusion (glomerular filtration rate = 30 to 75 ml per min). The study was preceded by 4 days of equilibration (dietary sodium 40 mmoles per day), and the drugs were alternated via a single-blind, cross-over protocol after a wash-out period of 3 days
Comparison of the effects of muzolimine and a fixed combination of diuretics in essential hypertension. The efficacy and tolerance of the loop diuretic muzolimine were compared with those of a fixed combination of hydrochlorothiazide and amiloride in patients with mild to moderate hypertension. After a placebo lead-in period, patients whose supine diastolic blood pressure was between 90 and 115 mm Hg were randomly allocated either to muzolimine, 20 mg/day, or to hydrochlorothiazide, 50 mg/day, and amiloride, 5 mg/day. The mean duration of follow-up was 4.7 months in both groups. Both muzolimine and the combination significantly decreased the mean blood pressure. The two treatments were similar in efficacy. The incidence of side effects during the trial was similar with both treatments
The diuretic effect of muzolimine (Bay g 2821) on hepatogenic ascites. A double-blind study was carried out in 22 patients with hepatogenic ascites to examine the effectiveness of the combination of muzolimine and spironolactone in comparison with combinations of furosemide and spironolactone and placebo and spironolactone. Despite the heterogeneous and variable case material , there was no significant difference between the 3 patient groups prior to treatment. After a diuretic-free preliminary period, all patients received 300 mg spironolactone daily plus 80 mg muzolimine, 80 mg furosemide or placebo for 7 days. Before the start of treatment and at daily intervals, measurements were made of waist size, body weight, and urinary and electrolyte elimination. Blood chemistry was investigated
Comparison of the effects of muzolimine and furosemide in patients with end-stage renal failure on chronic dialysis. The pharmacodynamic effects of muzolimine and furosemide were compared in a single dose cross-over study in 8 patients on regular dialysis treatment, who had a residual diuresis of more than 300 ml/day. The study periods comprised two dialysis-free intervals of 3 days . On the second dialysis-free day either muzolimine 240 mg or furosemide 240 mg was administered orally. Urine was collected in 12-h periods on the pre-treatment, treatment and post-treatment days, and the excretion of sodium, potassium, urea and creatinine were measured. After administration of muzolimine 240 mg urine volume rose to twice that of the previous day, and sodium excretion increased approximately
Muzolimine and nitrendipine in the treatment of arterial hypertension. Thirty patients with moderate to severe hypertension (diastolic blood pressure greater than or equal to 115 mmHg), after a run-in wash out period of 15 days, were treated with muzolimine at a dosage of 20 mg once daily, given at 1 p.m., for three weeks. At the end of this period of treatment the patients with diastolic blood with diastolic blood pressure greater than or equal to 100 mmHg were treated with a triple combination: muzolimine plus nitrendipine plus captopril at the same dosage for a further four weeks. At the end of run-in and of each period of treatment blood pressure and heart rate were recorded in supine and erect positions and after a treadmill exercise test. At these times laboratory tests, including PRA
Interference on metabolism induced by muzolimine and chlorthalidone in type II hypertensive diabetics. There is a very high prevalence of hypertension in diabetic subjects, which makes it necessary to use an antihypertensive drug with the least possible metabolic interference. For example, in the early phase of hypertension, diuretics usually worsen the metabolic equilibrium. According to recent reports, a new diuretic, muzolimine (MZ), which acts on the loop of Henle, seems to present a minor effect on carbohydrate metabolic balance. In order to determine whether this assumption was correct or not, we carried out a clinical trial on 26 type II (non-insulin-dependent) diabetics, in fairly good metabolic control and with moderate hypertension (orthostatic diastolic pressure from 100 to 115 mmHg
Comparative pharmacodynamics of furosemide and muzolimine in cirrhosis. Study on renal sodium and potassium handling and renin-aldosterone axis. Ten male cirrhotic patients with ascites and reduced renal function were randomly given equivalent doses of furosemide and muzolimine by the oral route, through a single blind cross-over protocol. Renal function, electrolyte plasma concentrations and urinary excretions and renin-angiotensin-aldosterone system components were evaluated under basal conditions and after drug administration. The diuretic and saluretic effects being equal, the response to muzolimine was initially weaker but more prolonged than to furosemide, without rebound phenomena. The furosemide-induced natriuresis was in part related to the filtered sodium load, whereas muzolimine
Comparative study of muzolimine and acebutolol in the treatment of moderate hypertension. In a controlled double-blind study the effect of muzolimine (20 mg o.d.) and acebutolol (400 mg o.d.) were investigated in outpatients suffering from moderate essential hypertension. After a three week placebo run-in period, 49 patients were recruited and followed by a cooperative group of general
Treatment of mild to moderate essential hypertension with muzolimine. Two years of follow-up. This study was carried out in association with medical practitioners who were responsible for observing the patients. In a first phase, 58 subjects younger than 70 years with moderate essential hypertension were allotted at random to treatment with either indapamide (2.5 mg per day) or muzolimine (20 mg per day). The double blind-double dummy study lasted for six months and demonstrated that the two drugs were similar in efficacy and tolerance. At the end of this phase 42 patients whose supine diastolic blood pressure fell to below 100 mmHg were selected to continue the trial with 20 mg per day muzolimine in an open long-term study. The survey comprised two periods: the first lasted for six months
Efficacy of two different doses of muzolimine in the treatment of mild hypertension. A report is given on the effects of oral therapy with muzolimine (M) in patients with mild hypertension. 21 untreated patients, aged 35 to 69 (mean 53.1 yrs) with orthostatic diastolic BP between 100 and 115 mmHg were randomly assigned to either group A (10 mg M/day) or group B (20 mg M/day) in a single blind significantly reduced in group A whereas only orthostatic diastolic BP was decreased in group B (Fig. 1). PRA and aldosteronemia values and blood chemistry showed no statistically significant changes. No side effects were noted. We conclude that 10 mg/day of muzolimine is more effective than 20 mg/day in reducing orthostatic diastolic BP (A vs. B p less than 0.02). Although these results are only preliminary
Cross-over study of muzolimine and hydrochlorothiazide-amiloride in hypertensive patients. Thiazide therapy is a widely used first line treatment for arterial hypertension. Its useful value, particularly in mild or moderate hypertension, is sometimes reduced by metabolic side-effects, as hypokalaemia and hyperuricaemia. In the present study the antihypertensive efficacy of a new, non-sulphonamide diuretic Bay g 2821 (muzolimine) was evaluated in comparison with the combination of hydrochlorothiazide-amiloride over a period of 4 weeks. A highly significant decrease in systolic and diastolic blood pressures was produced by both treatments. No decrease in serum potassium nor an increase in cholesterol, triglycerides, uric acid or glucose was detected during the 4 week treatment period. Subjective
Clinical evaluation of muzolimine and indapamide during treatment for essential hypertension. Muzolimine, a new saliuretic, has been shown to combine high ceiling and long-acting effects in animal experiments. This study was designed to examine whether this desirable combination of effects, which up until the present time has not been incorporated into any substance also occurs during patient treatment. Fifty-three patients with mild essential hypertension (WHO groups I and II) in three medical centers were treated with either muzolimine or indapamide, which served as the reference preparation, in a randomised, double-blind study. After a two week run-in phase during which the patients received placebo, half of the patients received 20 mg muzolimine and the other half 2.5 mg indapamide once
Haemodynamic studies with muzolimine in left ventricular failure complicating acute myocardial infarction. This is an interim report of haemodynamic studies with oral muzolimine in male patients under 70 yr with haemodynamically confirmed left ventricular failure complicating acute myocardial infarction. All were in sinus rhythm and without hypotension (SBP 100 mmHg) and were studied by conventional intravascular haemodynamic methods within 18 hr of onset of symptoms of acute myocardial infarction. A preliminary dose-finding study in four patients indicated that both 60 and 120 mg oral muzolimine induced substantial diuresis but only the latter dose was associated with an appreciable reduction in left heart filling pressure within 2 hr. The aims of the main study are to determine
The effects of single doses of muzolimine upon urinary solute and fluid excretion. The natriuretic effect of many loop diuretics is followed by an important decrease - rebound undershoot - in renal Na+ excretion, which is accompanied by thirst and fluid reposition. Also most loop diuretics increase K+ and Mg2+ urinary outputs, thus leading to somatic depletion of these cations and subsequent cardiac arrhythmias. The objectives of the present study were to describe the urinary outputs and flows of several solutes after various doses of muzolimine. Experiments were carried out in ten healthy adult volunteers given monodoses of placebo and of muzolimine 20, 30 and 40 mg on separate days and in random order. Urine collected at 3, 6, 9, 12 and 24 h after dosing was analysed for solutes
Effects of haemodialysis on the pharmacokinetics of muzolimine. High ceiling diuretics allow a better control of fluid balance in dialysis patients with a minimum urine flow of 500 ml/day. The pharmacokinetics of the high ceiling, long acting diuretic muzolimine (M) was investigated in 6 patients on regular dialysis therapy. Concentrations of unchanged M in plasma were determined by high