PMID- 8156396
OWN - NLM
STAT- MEDLINE
DCOM- 19940518
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 634
IP  - 1
DP  - 1994 Jan 14
TI  - 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.
PG  - 96-104
AB  - 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)
FAU - Gordon, J T
AU  - Gordon JT
AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia 19104.
FAU - Martens, D A
AU  - Martens DA
FAU - Tomlinson, E E
AU  - Tomlinson EE
FAU - Greenberg, J
AU  - Greenberg J
FAU - Dratman, M B
AU  - Dratman MB
LA  - eng
GR  - MH44210/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Iodine Radioisotopes)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - Q51BO43MG4 (Thyroxine)
RN  - TG537D343B (Desipramine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Desipramine/*pharmacology
MH  - Iodine Radioisotopes
MH  - Male
MH  - Norepinephrine/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Synaptosomes/*drug effects/metabolism
MH  - Thyroxine/*metabolism
MH  - Triiodothyronine/*metabolism
EDAT- 1994/01/14 00:00
MHDA- 1994/01/14 00:01
CRDT- 1994/01/14 00:00
PHST- 1994/01/14 00:00 [pubmed]
PHST- 1994/01/14 00:01 [medline]
PHST- 1994/01/14 00:00 [entrez]
AID - 0006-8993(94)90262-3 [pii]
AID - 10.1016/0006-8993(94)90262-3 [doi]
PST - ppublish
SO  - Brain Res. 1994 Jan 14;634(1):96-104. doi: 10.1016/0006-8993(94)90262-3.