Effect of Anti‐thyroid Agents, Methimazole and Propylthiouracil, on Brain Noradrenaline Content

Abstract

1Methimazole (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 [3H1-noradrenaline ([3HI-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 /-hydroxylase.

Methimazole Inhibits the Expression of GFAP and the Migration of Astrocyte in Scratched Wound Model In Vitro

“…The capability of methimazole to attenuate the direct inflammatory response suggested an anti-inflammatory role. As mentioned above, methimazole has been found to inhibit the glial cell function in a diabetic mouse model [14]. Our results were consistent with these previous results.…”

“…Methimazole is an antithyroid compound that has been broadly used in the treatment of hyperthyroidism and Graves disease via preventing the production of the level of thyroid hormones from the thyroid gland. Interestingly, methimazole was also found to have significant impact on CNS by influencing the levels of varieties of neurotransmitters [14]. A previous study also suggested that methimazole could regulate the opioid receptor expression in the brain [15].…”

Inhibition of Dopamine β-Hydroxylase by Goitrin, a Natural Antithyroid Compound

“…Increases in adrenal, cardiac, and brain DA and decreases in brain NE following the administration of DBH inhibitors are well documented (17)(18)(19). Further, DA increases following the administration of DBH inhibitors have been related to the ability of such inhibitors to prevent the conversion of 23H-DA to 3H-Ne (17), indicating that tissue DA increases and NE decreases were at least in part due to the ability of the inhibitor to produce in vivo DBH inhibition.…”

Study on the induction of thyroid tumors in rats using x irradiation in conjunction with a goitrogen. [1 methyl--2 mercaptoimidazole (methimazole)]

“…I t has a1 so been reported (Hashizume and Yamaki , 1977) of Lindsay e t a1 . (1 966, 1968a), Lindsay -(-1969), and Doniach ( 7 970, 1 974) .…”