PMID- 8035306
OWN - NLM
STAT- MEDLINE
DCOM- 19940815
LR  - 20151119
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 270
IP  - 1
DP  - 1994 Jul
TI  - An acute dose of desmethylimipramine inhibits brain uptake of 
      [125I]3,3',5-triiodothyronine (T3) in thyroxine-induced but not T3-induced 
      hyperthyroid rats: implications for tricyclic antidepressant therapy.
PG  - 111-7
AB  - The tricyclic antidepressant, desmethylimipramine (DMI), a highly selective 
      inhibitor of presynaptic uptake of norepinephrine (NE), has also been shown to 
      reduce [125I]3,3',5-triiodothyronine (T3) uptake in rat brain synaptosomes. Using 
      DMI as a probe to examine 1) possible noradrenergic influences on thyroid hormone 
      (TH) actions in brain and 2) TH:affective disorder relationships, we found that a 
      single dose of DMI produces a small (7.4-25%) but significant (P < or = .05) 
      decrease in brain uptake of both labeled T3 (T3) and labeled thyroxine (T4) 
      across the spectrum of thyroid states from hypothyroid (HYPO) to euthyroid to 
      T4-induced hyperthyroid. Therefore, it was noted with considerable interest that 
      DMI appeared not to interfere with brain T3 uptake in T3-induced hyperthyroid 
      (T3-HYPER) rats. To confirm this finding, thyroidectomized male rats were made 
      T3-HYPER through administration of T3 (20 micrograms/kg) for 3 weeks or 
      maintained without TH supplement for 6 weeks, becoming HYPO. Rats were given i.v. 
      T3 and 5 min later i.p. DMI or saline. They were decapitated at 3 hr and brains 
      retrieved for radiochemical analysis. Each experiment was run in three separate 
      trials, with three to four rats in each treatment category (DMI or saline). 
      Evaluation by analysis of variance showed that T3 concentrations (percentage of 
      dose) were significantly lower in DMI than in saline-treated rat brain for HYPO 
      (-15%; P = .0034) but not T3-HYPER rats (-2%; P = .6595). These results suggest 
      that, as it does in the case of NE, DMI tends to block TH uptake sites in rat 
      brain. The data also demonstrate a differential affinity for those sites in which 
      T3 > DMI > T4 and suggest that T3 might augment tricyclic antidepressant therapy 
      more effectively than T4.
FAU - Gordon, J T
AU  - Gordon JT
AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia.
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
GR  - MH45252/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  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Iodine Radioisotopes)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - EC 1.11.1.8 (Iodide Peroxidase)
RN  - F604ZKI910 (Ipodate)
RN  - Q51BO43MG4 (Thyroxine)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/*therapeutic use
MH  - Brain/*drug effects/enzymology/*metabolism
MH  - Desipramine/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Hyperthyroidism/chemically induced/drug therapy/*metabolism
MH  - Hypothyroidism/drug therapy/metabolism
MH  - Iodide Peroxidase/antagonists & inhibitors
MH  - Iodine Radioisotopes
MH  - Ipodate/pharmacology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thyroxine/pharmacokinetics/*pharmacology
MH  - Time Factors
MH  - Triiodothyronine/*pharmacokinetics/pharmacology
EDAT- 1994/07/01 00:00
MHDA- 1994/07/01 00:01
CRDT- 1994/07/01 00:00
PHST- 1994/07/01 00:00 [pubmed]
PHST- 1994/07/01 00:01 [medline]
PHST- 1994/07/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1994 Jul;270(1):111-7.