Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine uptake, has diverse effects on thyroid hormone processing in rat brain. II. Effect on in vivo 5'-deiodination of [125I]thyroxine.
We have studied the effects of desmethylimipramine (DMI), a tricyclic antidepressant, on thyroid hormone (TH) handling in rat brain in an effort to discover a pharmacological basis for reported interactions between TH, affective disorders and psychotropic drugs. An acute dose of DMI has been used in order to determine the primary effects of the drug in brain without perturbations from secondary effects. Recently we have reported that a single dose of DMI significantly decreases brain uptake of both [125I]thyroxine (T4) and [125I]3,3',5-triiodothyronine (T3) across the spectrum of thyroid states from hypothyroid (HYPO) to euthyroid (EU) to T4-induced hyperthyroid (HYPER). To investigate further the effects of DMI on brain processing of TH, we have measured effects of the drug on in vivo rates of T4 to T3 conversion in a series of experiments in which DMI (25 mg/kg) was given to HYPO, EU and HYPER male rats in conjunction with i.v. [125I]T4. Decreased in vivo conversion ratios (T3/T4 ratios) suggest that acute DMI treatment causes a significant decrease in 5'-deiodinase activity in balance of brain (but not cerebellum) in all DMI treated rats as compared to their saline treated controls (ANOVA, P < 0.0001). For assurance that reduced T3/T4 in DMI treated rat brain is not the result of DMI enhancement of 5-deiodination of T3 or T4, the effect of DMI on concentrations of labeled I-, rT3, and T2 (3,3'- and 3',5'-) was also observed. In no case was there a significant increase in any metabolite in DMI treated rats for any tissue studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Gordon
J T
JT
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104.
Martens
D A
DA
Tomlinson
E E
EE
Greenberg
J
J
Dratman
M B
MB
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D013974:Thyroxine; D003891:Desipramine; D009638:Norepinephrine