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EFFECT OF ANTI‐THYROID AGENTS, METHIMAZOLE AND PROPYLTHIOURACIL, ON BRAIN NORADRENALINE CONTENT
Author(s) -
HASHIZUME Y.,
YAMAKI T.,
HIDAKA H.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb06990.x
Subject(s) - propylthiouracil , endocrinology , medicine , methimazole , chemistry , endogeny , in vivo , intraperitoneal injection , dopamine , antithyroid agent , thiouracil , thyroid , biology , microbiology and biotechnology , graves' disease
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 [ 3 H]‐dopamine into [ 3 H]‐noradrenaline ([ 3 H]‐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 β‐hydroxylase.