RENAL ACTIVITY AND PHARMACOLOGY OF N-ACYL AND RELATED SULFONAMIDES

¹ Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, Florida

The N⁷-acetyl derivatives of chlorothiazide and hydrochlorothiazide are not hydrolyzed (<0.1%) to their parent drugs in vito following intravenous injection. They do elicit the renal "saluretic" response typical of the thiazide drugs, of which hydrochlorothiazide at 1 to 5 mg/kg is a prototype: nearly equal excretion of sodiun and chloride ions; slight potassium excretion; acidification of the urine. A similar pattern follows administration of 7-methylsulfonyl-chlorothiazide.

These three compounds are not carbonic anhydrase inhibitors; these experiments therefore dissociate the "saluretic" pattern from that of carbonic anhydrase inhibition. Whereas a R—SO₂NH₂ group is essential for inhibition of this enzyme, the requirements for saluresis are less rigid.

N⁷-acetylchlorothiazide is similar to chlorothiazide with respect to renal clearance and distribution; on a weight basis it is far less active. It has the same mechanism of saluretic action as the conventional thiazide drugs.

Correlation of present with previous data shows that aromatic compounds of the type R—SO₂NH-acyl and R—SO₂NH-alkyl are susceptible to cleavage in vivo to yield the free sulfonamides, with the important exception of the acetyl derivatives.