THE PHARMACOLOGY OF TRICHLORMETHIAZIDE, A BENZOTHIADIAZINE DIURETIC

¹ Department of General Pharmacology, Biological Research Division, Schering Corporation, Bloomfield, New Jersey, and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

The 3-dichloromethyl derivative of hydrochiorothiazide, trichiormethiazide, was found to be an effective diuretic which, on an oral dose basis in animals, was 10 times more potent than hydrochlorothiazide and 60 times more potent than chlorothiazide. It caused a pronounced increase in sodium and chloride excretion in a molar ratio of 1:1. Potassium, hydrogen ion and ammonium excretion were increased to a slight extent. Five-hour studies in dogs demonstrated that maximum saluretic effects can be achieved at oral doses of 0.5 mg/kg.

Trichlormethiazide is secreted by the renal tubules. However, since the drug is extensively bound to plasma proteins, its renal clearance is substantially less than the clearance of hydrochlorothiazide or chlorothiazide. In vitro experiments showed that trichiormethiazide is a relatively weak carbonic anhydrase inhibitor with an order of potency similar to that of hydrochlorothiazide.

In dogs receiving daily oral doses of trichiormethiazide for 1 year, the only adverse effect noted was a moderate decrease in the plasma potassium concentration at doses of 500 mg/kg per day.