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. Muzolimine 20 mg did not increase mean 24 h urinary Na+ output significantly with respect to placebo. Muzolimine 30 mg exerted maximal diuretic, chloriuretic and natriuretic effects, while not affecting the mean 24 h urinary outputs of K+ and Mg2+ significantly. Muzolimine 30 mg caused a small undershoot in urinary Na+ flow after completion of its natriuretic effect. Muzolimine 30 mg should be considered a first choice loop diuretic since it only causes a mild post-natriuretic undershoot and does not increase urinary Mg2+ output significantly.