A New Diuretic Drug Dependent on the Adrenal for its Action

Abstract

2- [2,6-Diphenyl-4 (1-pyrrolidinyl) cyclohexyl] - pyridine (Su- 15049) caused marked natriuresis and water diuresis in rats without consistent effects on potassium excretion. Its natriuretic actions were abolished by adrenalectomy. In adrenalectomized animals Su-15049 did not modify the response to aldosterone except when the latter was given in the massive doses (0.5 mg/rat) expected to have some glucocorticoid-like effects. Cortisol or corticosterone, however, made adrenalectomized animals responsive to Su-15049, and the presence of cortisol permitted the drug to antagonize the Na-retaining effects of aldosterone. No corticoid substitution therapy was found, however, that enabled adrenalectomized animals to respond to Su-15049 in regard to potassium excretion precisely as did normal ones. Su-15049 has some activity in conventional anti-inflammatory tests.