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THE EFFECTS OF VARIOUS CHLORINE DERIVATIVES OF THYRONINE ON SERUM CHOLESTEROL CONCENTRATION AND MYOCARDIAL STIMULATION IN RATS AND HUMANS

W. F. J. CUTHBERTSON, PH.D.^*, P. V. ELCOATE^*, D. M. IRELAND^*, D. C. B. MILLS^*, G. S. BOYD, PH.D. and M. F. OLIVER, M.D.

Glaxo Laboratories Ltd., Greenford, Middlesex, England; and the Department of Biochemistry, University of Edinburgh and Department of Cardiology Royal Infirmary, Edinburgh

Chlorinated and iodinated thyronine derivatives were studied for their effects on serum and liver cholesterol and on hypertrophy of the cardiac ventricle, in the rat. Compounds characterized by higher ratios of cholesterol to cardiac effects were found among the derivatives with the D-configuration and with chlorine atoms in the 3 and 5 positions. In the rat, some compounds—notably 3:5-dichloro-3':5'-diiodo-D-thyronine (DCl₂I₂T) and 3:5:3'-trichloro-5'-iodo-D-thyronineDCl₃IT)—exerted a much greater effect on cholesterol metabolism than on the myocardium. DCl₂I₂T, 3:5:3'-trichloro-D-thyronine (DCl₃T) and 3:5-dichloro-D-thyronine (DCl₂T) were administered to 30 hypercholesterolemic men with coronary heart disease. Although DCl₂I₂T produced no significant reduction of serum cholesterol concentration, DCl₃T and DCl₂T did; and all 3 substances caused symptoms of myocardial stimulation, usually angina. Therefore none of these compounds is regarded as suitable for administration to patients with coronary heart disease. DCl₃T and DCl₂T produced striking depression of the serum protein-bound iodine level, and this effect is discussed.

^* Glaxo Laboratories, Greenford, Middlesex, England.

Dept. of Biochemistry, University of Edinburgh, Scotland.

Dept. of Cardiology, Royal Infirmary, Edinburgh, Scotland.

Received May 19, 1961.