Effect of anti-thyroid agents, methimazole and propylthiouracil, on brain noradrenaline content.

1 Methimazole (1-methyl-2-mercaptoimidazole, MMI) and propylthiouracil (6-propyl-2-thiouracil, PTU) which are used in the therapy of hyperthyroidism were found to reduce brain noradrenaline (NA) content. Endogenous NA levels in rat brain were reduced from 1 to 6 h after intraperitoneal injection of MMI by doses in excess of 25 mg/kg and by PTU at a dose of 50 mg/kg. However, endogenous NA in the rat heart was only slightly reduced after 50 mg/kg of MMI, and was not affected by PTU (50 mg/kg). 2 Both MMI and PTU effectively inhibited the in vivo conversion of [3H]-dopamine into [3H]-noradrenaline ([3H]-NA) in the brain of rats after a single intraperitoneal injection of doses above 10 mg/kg (MMI) and 25 mg/kg (PTU). This inhibition by MMI and PTU was dose-dependent over the range of 10 mg/kg to 50 mg/kg, was highest after 2-3 h and continued for at least 6 h after their injection; The conversion rates returned to normal after 24 hours. 3 The results suggest that the reduction of brain NA by these drugs is, at least in part, due to the inhibition of brain dopamine beta-hydroxylase.