Synthesis and effects on peripheral thyroid hormone conversion of (R)‐4‐hydroxypropranolol, a main metabolite of (R)‐propranolol

Abstract

The inhibiting effect of (R,S)-propranolol on peripheral T4E3 conversion can be related to the (R)-isomer. The intention of this study is to clarify if (R)-4-hydroxypropranolol, a main metabolite of (R)-propranolol, develops the same or even a stronger effect on peripheral thyroxine metabolism as the parent drug. (R)-4-hydroxypropranolol was synthesized via (R)-4-methoxypropranolol and their optical purity was checked chromatographically. Twenty patients suffering from hyperthyroidism were divided into five groups and treated with (Rb4-h~-droxypropranolol HC1 in dosages from 12 to 75 mg per day in a placebo controlled study over a period of 5 days. The serum hormone levels and resting pulse rate were measured. No significant changes of thyroid parameter could be observed but a significant decrease of resting pulse rate under treatment with 75 mg (R)-4-hydroxypropranolol occurred. It could be concluded that (R)-4-hydroxypropran-0101 possesses negative chronotropic effects but develops no changes in thyroid hormone metabolism in hyperthyroid patients.KEY WORDS: hyperthyroidism, (R)-4-hydroxypropranolol, peripheral conversion, metabolites of propranolol, negative chronotropic effect