The present work studied the effects of amiodarone (AMD) and iopanoic acid (IA) on the conversion of thyroxine (T ₄ ) to tri-iodothyronine (T ₃ ) by rat myocardium. In vivo : male Wistar rats weighing 200–250 g were injected i.p. with AMD (2·5 mg/100 g body weight per day for 12 days) or IA (5 mg/100 g body weight every 12 h for 72 h). Hearts were then removed and processed as in the in-vitro studies. In vitro : hearts were homogenized in Krebs–Ringer phosphate buffer (pH 7·4) and AMD (0·1 mmol/l) or IA (10 mmol/l) plus dithiothreitol (8 mmol/l) and 0·01 μCi [ ¹²⁵ I]T ₄ or [ ¹²⁵ I]T ₃ were added. After incubation for 2 h at 37 °C, radioactive compounds were identified by paper chromatography. Both AMD and IA given in vivo blocked T ₄ to T ₃ conversion significantly ( P <0·005). When added in vitro , AMD failed to inhibit T ₄ deiodination to T ₃ whereas IA induced a significant ( P <0·005) decrease in T ₃ generation. Deiodination of [ ¹²⁵ I]T ₃ by heart homogenates was not altered by AMD or IA. While the expected increase in circulating T ₄ ( P < 0·001) and decrease in T ₃ ( P < 0·001) did occur after AMD or IA treatment, plasma TSH in AMD-treated rats was decreased ( P <0·001), while in IA-treated animals it was increased ( P < 0·001), thus indicating that AMD did not inhibit pituitary type-II 5′-monodeiodinase.

In summary, these data suggest that the hypometabolism induced by AMD in rat myocardium through a decrease in the supply of T ₃ is not responsible for the anti-arrhythmic activity of this drug since IA, which is not an anti-arrhythmic compound, elicited the same effect on cardiac T ₃ . It follows that inhibition of 5′-deiodinase and the anti-arrhythmic activity of AMD are independent properties.

Journal of Endocrinology (1989) 121, 431–434