A. A. Renzi

Sulfonamide compounds with high diuretic activity

Abstract Several related compounds are more active than chlorothiazide in enhancing water, sodium, and, generally, potassium excretion in rats. Of these, hydrochlorothiazide had from seven to twenty-one times the potency of chlorothiazide, depending upon the parameter measured and conditions of test. After administration of the drug, an increased rate of sodium excretion preceded marked change in water excretion. Hydrochlorothiazide modified renal response to vasopressin, reserpine, syrosingopine, aldosterone, DCA, and prednisolone and to adrenalectomy. It did not modify the hypertensive response to hydrocortisone but did inhibit blood pressure rise in adrenal regeneration hypertension when given chronically, but not acutely.

Distribution and fate of hydrochlorothiazide-H3

Abstract Hydrochlorothiazide was labeled with tritium by the reduction of chlorothiazide with tritium-labeled sodium borohydride. Its distribution and metabolism were studied in saline-loaded, fasted rats. The drug was rapidly absorbed and 43 and 69% was excreted into the urine in 48 hours with doses of 4.7 and 0.15 mg/kg, respectively. No evidence could be found for the metabolic alteration of hydrochlorothiazide by the rat.

ACTH-suppressing action of aldosterone.

Summary Crystalline aldosterone suppressed the release of pituitary ACTH in animals exposed to the stress of cold as judged by adrenal ascorbic acid determinations. Its activity in this respect approximated one-third that of cortisone and eight times that of desoxycorticosterone

Interaction of methandrostenolone and adrenocortical hormones.

Summary The anabolic steroid methan-drostenolone partially antagonized the growth inhibiting effects of glucocorticoids in rats and also, depending on the type of experiment, augmented or added to the anti-inflammatory activity of these steroids. Similar activity was found with methyltestosterone and testosterone, whereas norethandrolone and progesterone were inactive. The action of methandrostenolone was independent of the adrenal. Methandrostenolone itself showed no other signs of glucocorticoid-like activity. The authors wish to express their appreciation to Dr. Robert Gaunt for advice and encouragement and to Mrs. Hanna Sylwestrowicz for statistical evaluation. Thanks are due also to Nancy Howie, Margot Stein, Patricia Reilly and Viola Dube for technical assistance.

A new diuretic drug dependent on the adrenal for its action.

Summary 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.