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Abstract

Aquaretic effect of a potent, orally active, nonpeptide V2 antagonist in men.

A Ohnishi, Y Orita, N Takagi, T Fujita, T Toyoki, Y Ihara, Y Yamamura, T Inoue and T Tanaka
Journal of Pharmacology and Experimental Therapeutics February 1995, 272 (2) 546-551;
A Ohnishi
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Y Orita
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N Takagi
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T Fujita
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T Toyoki
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Y Ihara
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Y Yamamura
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T Inoue
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T Tanaka
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Abstract

Solute-free water diuretics (aquaretics) that antagonize hydrosmotic vasopressin 2 (V2) receptors may be useful in treating diseases in which water is retained. An orally active, nonpeptide, selective V2 antagonist (OPC-31260) was administered in six dose steps (3, 15, 30, 60, 100 and 200 mg) to six healthy, normally hydrated men to investigate the aquaretic effects in comparison with 12 placebo-treated control subjects (two at each dose). All subjects tolerated all six doses without serious clinical side effects. OPC-31260 increased the first 6-hr hypotonic urine volume dose-dependently. Administration at 30 mg raised the 6-hr urine volume to 2 times, 100 mg to 3 times and 200 mg to 4 times (1828.0 +/- 130.2 ml/6 hr) that of the placebo group (470.4 +/- 52.1 ml/6 hr). The drug increased urine flow maximally between 1 and 1.5 hr at all doses (e.g., 10.0 +/- 0.7-10.8 +/- 0.4 ml/min at 60-200 mg). The drug rapidly lowered urine osmolality for 4 hr, particularly between 60 and 90 min (e.g., 72.3 +/- 2.3 and 62.3 +/- 5.1 mOsm/kg at 100 and 200 mg, respectively). In marked hypotonic diuresis, mean free-water clearance of the 6-hr urine increased dose-proportionally into the positive range, reaching 2.82 +/- 0.21 ml/min at 200 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 272, Issue 2
1 Feb 1995
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Abstract

Aquaretic effect of a potent, orally active, nonpeptide V2 antagonist in men.

A Ohnishi, Y Orita, N Takagi, T Fujita, T Toyoki, Y Ihara, Y Yamamura, T Inoue and T Tanaka
Journal of Pharmacology and Experimental Therapeutics February 1, 1995, 272 (2) 546-551;

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Abstract

Aquaretic effect of a potent, orally active, nonpeptide V2 antagonist in men.

A Ohnishi, Y Orita, N Takagi, T Fujita, T Toyoki, Y Ihara, Y Yamamura, T Inoue and T Tanaka
Journal of Pharmacology and Experimental Therapeutics February 1, 1995, 272 (2) 546-551;
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