Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muzolimine is a diuretic which has been proposed in the treatment of hypertension. Muzolimine shared both the high ceiling effect of loop diuretics and the long duration of action of thiazides but has a chemical structure different from those of other loop diuretics. It may act as a prodrug and an active metabolite present in the urine may inhibit NaCl reabsorption in the Henle's loop. We studied the effect of urines of piretanide and muzolimine treated rats on Na+K+Cl- cotransport in renal cells in culture (MDCK). In the presence of ouabain (0.5 mM), the Na+K+Cl- cotransport measured by 86Rb influx, represented 92 p.100 of the total 86Rb influx (6.16 +/- 1.12 nmol 86Rb/min/mg prot, n = 10). Both diuretics were administered i.v. to rats where they induced marked diuresis. Excreted urine (dilution to 1/100) was tested for cotransport inhibition. After piretanide (27 mumol/kg) the urine inhibited the Na+K+Cl- cotransport in MDCK cells (72% and 41% inhibition at the 15th and 45th minutes after diuretic injection). After muzolimine (50 mumol/kg), urines also inhibited Na+K+Cl- cotransport but the effect was slower in onset and more prolonged (42% and 49% inhibition at the 15th and 60th min). Diuretic effects in vivo and Na+K+Cl- cotransport inhibition in vitro by the urine developed parallel for both diuretics. Probenecid (100 mumol/kg) suppressed simultaneously the diuretic effect of muzolimine and the Na+K+Cl- cotransport inhibition by the urine of muzolimine treated rats. Our results suggest that muzolimine acts as a prodrug. Its active metabolite is secreted into the tubular lumen through a probenecid sensitive pathway and inhibits, like other loop diuretics, Na+K+Cl- cotransport.
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PMID:[Mechanism of action of the diuretic effect of muzolimine]. 212 57

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, and no serious adverse reactions occurred. Eleven subjects in the muzolimine group were entered into an open long-term study. In all these subjects the blood pressure remained adequately controlled throughout the 4 to 6 months of additional follow-up and no side effects were reported. Muzolimine appears to be an effective and safe antihypertensive agent.
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PMID:Comparison of the effects of muzolimine and a fixed combination of diuretics in essential hypertension. 351 11

27 patients with creatinine clearances ranging from 20 to 2 ml/min were treated daily with 6.9 mg/kg of muzolimine, for 10 to 25 days. The hyperhydration state with oedema decreased gradually in all patients without hypotensive phenomena. Muzolimine benefited hypertension in patients with expansion of the extracellular space and it also strengthened the effect of clonidine or minoxidil. Important diuretic and natriuretic effects were obtained. Metabolic acidosis improved. No subjective adverse reactions to the drug or side effects were noted. High-dose muzolimine appears to be efficacious and safe for short-term treatment in patients with severe chronic renal failure.
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PMID:Muzolimine in advanced chronic renal failure. 400 83

Muzolimine was administered by mouth to 24 patients with creatinine clearances ranging from 4 to 28 ml/min to treat oedema or hypertension, or both. In four of these 24 patients muzolimine was given after intravenous high-dose frusemide had been unsuccessful. Muzolimine significantly increased urine volume and excretions of sodium, chloride, and potassium ions. Its diuretic efficacy was further shown by a mean reduction in body-weight of 8% and by the disappearance of oedema in all affected patients, even those refractory to intravenous frusemide. No rebound phenomenon was observed after the drug was stopped. Mean blood pressure was reduced in all hypertensive patients. Blood pressure was restored to normal in five out of seven patients treated with muzolimine alone and 10 out of 11 in whom muzolimine had been added to previously unsatisfactory antihypertensive treatment. Muzolimine was well tolerated by all patients. Muzolimine appears to be the diuretic of choice when treating patients with advanced renal disease.
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PMID:Muzolimine: a new high-ceiling diuretic suitable for patients with advanced renal disease. 678 85