The effect of D,L-4-hydroxypropranolol on the thyroxine to 3,5,3'-triiodothyronine conversion in rat renal and liver microsomes.
The in vitro effect of D,L-4-hydroxypropranolol, a major pharmacological active metabolite of the beta adrenoceptor blocking drug D,L-propranolol, on the thyroxine (T4) to 3,5,3'-triiodothyronine (T3) conversion has been studied using rat renal and liver microsomal fractions. The results showed, that primarily the metabolite, but also the parent drug inhibits the T3-production in a dose dependent manner. The potency, expressed as the 50% inhibition of the T3-production, was reached using 65 +/- 12 (SD) microM D,L-4-OH-propranolol and 1000 +/- 22 (SD) microM D,L-propranolol, respectively in both tissues. The efficacy of 4-OH-propranolol corresponded to a maximal inhibition of 86 +/- 7% while it for D,L-propranolol corresponded to 58 +/- 6% (P less than 0.001). The beta adrenoceptor agonist isoprenaline itself did not effect the T4 to T3 conversion but considerably opposed the inhibitory effect of D,L-4-OH-propranolol but not of D,L-propranolol. The D-isomer form of propranolol, which is without beta receptor blocking activity inhibited the T3-production in the same degree as D,L-propranolol. Evaluation of the enzyme kinetic data suggested that 4-OH-propranolol caused a competitive inhibition of both T4 and DTT. It is concluded, that the metabolite D,L-4-OH-propranolol is a much more potent and efficacious inhibitor of the T4-5'-deiodination than D,L-propranolol.
D000818:Animals; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000096:biosynthesis*
D014284:Triiodothyronine; C001422:4-hydroxypropranolol; D011433:Propranolol; D007545:Isoproterenol; D013974:Thyroxine