SOME ASPECTS OF PHARMACOLOGICAL ACTIVITY OF BENZTHIAZIDE IN DOGS

¹ Macrobiology Department, Chas. Pfizer & Co., Groton, Connecticut

Benzthiazide is a potent nonmercurial diuretic and saluretic agent. It produced a maximal saluretic effect during the second or third hour after oral administration (0.125 and 2.0 mg/kg) and within the first 10 to 30 minutes after i.v. administration (0.4 mg/kg). The excretion of sodium was still increased in 4 to 6 hours after oral administration of benzthiazide (2.0 mg/kg).

Renal clearance studies with benzthiazide indicated that pronounced natriuretic and chloruretic effects were observed at 0.1 mg/kg i.v.; these effects were not further increased with an increase in dose up to 1.0 mg/kg whereas potassium excretion was further increased at 0.25 mg/kg and bicarbonate excretion at 0.25 and 1.0 mg/kg.

Benzthiazide increased sodium and chloride excretion in experimental alkalosis and acidosis. The excretion of bicarbonate was significantly increased by benzthiazide in alkalotic but not in acidotic dogs.

Stop-flow experiments indicated the ability of benzthiazide to enhance K⁺ transport in the distal segment. The Na⁺ transport appeared more likely to be inhibited in the proximal than in the distal segment.

The primary natriuretic and chloruretic effects of benzthiazide are considered not to be due to carbonic anhydrase inhibition, whereas the ability of benzthiazide to increase the excretion of bicarbonate at higher dose levels is a manifestation of its activity as a carbonic anhydrase inhibitor.