Laboratory and clinical observations on chlorazanil, a nonmercurial orally effective diuretic agent.

D RUGS to promote the excretion of water in edematous states of varied etiology form an essential part of the equipment of every practitioner. Although the common denominator of all types of edema appears to be sodium retention by the kidney, many factors may be operative; viz., cardiac failure, decreased renal function, excess salt-retaining steroids, excess antidiuretic hormone, serum electrolyte imbalance, etc. In view of the multiplicity of factors in pathogenesis, it is not strange that the investigator should explore a variety of agents capable of inhibiting the abnormal renal retention of salt and water. Attention was called for the first time by Lipschitz over 13 years ago’ to a new group of substances possessing diuretic effects. These were triazine derivatives which were toxic, but which furnished an objective for chemical development which has culminated in the development of chlorazanil (N-para-chlorophenyl 2,4 diamino s triazine hydrochloride). This compound possesses the strongest diuretic effect with the least toxicity and furnishes the subject for this report. The drug has been studied in men and dogs for its effect on the excretion of water and electrolytes and for its influences on renal hemodynamics. This includes the establishment of a dose response curve and subsequent calculation of its potency relative to a standard diuretic (meralluride or Mercuhydrin) as well as the clinical responses following chronic therapy. Additional studies have been made on the drug in combination with aminophylline. The rationale for this approach and its application to other diuretic agents have been previously elaborated.*-’