新Thiazide系利尿剤Penfluzideの利尿活性と作用機序について (利尿剤に関する研究-6,7-)

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Diuretic activity and mechanism of a new thiazido diuretic, Penfluzide was compared in rats and dogs to that of structurally similar diuretics, Bendroflumethiazide and Hydroflumethiazide. Penfluzide in an oral dose of 0.1_??_1.0mg/kg caused a strong and dose dependent increase in urine volume as well as in urinary excretion of Na+ and Cl- while that of K+ was only sightly increased in normal rats. In experimental acidotic, alkalotic, nephrotic and spontaneously hypertensive rats, almost the same strong natriuretic activities were seen with Penfluzide, the diuretic activities of the 3 diuretics in rats being in the order of: Penfluzide ≥Bendroflumethiazide>Hydroflumethiazide. In the renal clearance test in dogs, Penfluzide revealed a strong diuretic effect which was not induced by an increased renal plasma flow and ilomerularmfiltration rat by a decrease of sodium and water reabsorption in the tubule. In the renal stop flow test in dogs, the acting site of Penfluzide was observed mainly in the proximal tubule. Inhibition of rat renal Na+-K+-ATPase was not demonstrated with Penfluzide either in vivo or in vivo. Weak hypotensive effects were observed with this drug.
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