Nathaniel T. Kwit

Human assay of three new mercurial diuretic agents; a promising preparation for oral use.

Conclusions Three organic mercurial preparations possessing diuretic activity were assayed by the oral route against the Standard, mercuhydrin solution given intramuscularly, in patients with congestive failure. Of the three materials, the 3-chloro-mercuri-2-methoxy propylurea proved to be the most effective, producing with oral doses a diuretic response equivalent to results obtained by the conventional doses of intramuscular mercuhydrin. The diuretic potency of this compound when given orally is somewhat more than one-fourth of its potency by intramuscular injection, and by the latter route 4.3 times (in milligrams) as potent as intramuscular mercuhydrin. We are not aware of any mercurial diuretic with such a favorable ratio of intramuscular to oral potency, namely 4:1. In the case of the thiol compound we tested in this study, the ratio was 11.1. In another study(7) in which mercuhydrin was tested by the intramuscular and oral routes, this ratio was 24:1. There still remains the problem of gastrointestinal irritation. By the method employed in the bioassay, it was necessary to give the total dose at one time, in the case of the larger doses as many as 9 tablets. This, therefore, subjected the local irritant action to a rigorous test. As the results stand, it appears that approximately one-half of the population with congestive heart failure might be able to tolerate by the oral route doses of this compound which produce highly effective diuretic responses. This is as far as the investigation in clinical pharmacology has carried the problem. It is now necessary to establish the most satisfactory dosage plans for the use of this material by the oral route. If approximately one-half of the population can tolerate as many as 9 tablets given at one time without gastrointestinal distress, it may well turn out that by dividing this amount into several fractions taken at intervals during the day, satisfactory diuretic effects may be obtained with less interference from gastrointestinal symptoms. The protracted use of the material over periods of weeks and months may disclose other problems which are not revealed by the single dose bioassay method. It remains for clinical trials to decide these matters.

TRENDS IN CARDIOLOGY: CURRENT VIEWS ON THE ETIOLOGY AND TREATMENT OF HYPERTENSION†

Panelists: MILTON MENDLOWITZ, M.D., New York, N. Y. Attending Physician, The Mount Sinai Hospital; Assistant Clinical Professor of Medicine, Columbia University College of Physicians and Surgeons. DAVID S. BALDWIN, M.D., New York, N. Y. Assistant Professor of Medicine, New York University School of Medicine. MILTON L. KRAMER, M.D., New York, N. Y. Clinical Professor of Medicine, Cornell University Medical College; Attending Physician, New York Hospital; Director of Medicine, Hospital for Joint Diseases. ARGYRIOS GOLFINOS, M.D., New York, N. Y. Research Fellow in Human Pharmacology, Cornell University Medical College. JOHN H. LARAGH, M.D., New York, N. Y. Associate Professor of Clinical Medicine, Columbia University College of Physicians and Surgeons. Moderator: NATHANIEL T. KWIT, M.D., New York, N. Y. Attending Cardiologist and Chief of the Cardiac Clinic, Hospital for Joint Diseases; Associate Physician in the Cardiovascular Research Unit, Beth Israel Hospital; Associate Attending Physician and Electrocardiographer, Lebanon Hospital; Associate Cardiologist and Chief of the Cardiac Clinic, Jewish Memorial Hospital.