Journal article
AN ACUTE DOSE OF DESMETHYLIMIPRAMINE INHIBITS BRAIN UPTAKE OF [I-125] 3,3',5-TRIIODOTHYRONINE (T-3) IN THYROXINE-INDUCED BUT NOT T-3-INDUCED HYPERTHYROID RATS - IMPLICATIONS FOR TRICYCLIC ANTIDEPRESSANT THERAPY
The Journal of pharmacology and experimental therapeutics, v 270(1), pp 111-117
01 Jul 1994
PMID: 8035306
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The tricyclic antidepressant, desmethylimipramine (DMI), a highly selective inhibitor of presynaptic uptake of norepinephrine (NE), has also been shown to reduce [I-125]3,3',5-triiodothyronine (T-3) uptake in rat brain synaptosomes. Using DMI as a probe to examine I)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 less than or equal to .05) decrease in brain uptake of both labeled T-3 (T-3(.)) and labeled thyroxine (T-4(.)) across the spectrum of thyroid states from hypothyroid (HYPO) to euthyroid to T-4-induced hyperthyroid. Therefore, it was noted with considerable interest that DMI appeared not to interfere with brain T-3(.) uptake in T-3-induced hyperthyroid (T-3-HYPER) rats. To confirm this finding, thyroidectomized male rats were made T-3-HYPER through administration of T-3 (20 mu g/kg) for 3 weeks or maintained without TH supplement for 6 weeks, becoming HYPO. Rats were given i.v. T-3(.) 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 T-3(.) concentrations (percentage of dose) were significantly lower in DMI than in saline-treated rat brain for HYPO (-15%; P = .0034) but not T-3-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 T-3 > DMI > T-4 and suggest why T-3 might augment tricyclic antidepressant therapy more effectively than T-4.
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- Title
- AN ACUTE DOSE OF DESMETHYLIMIPRAMINE INHIBITS BRAIN UPTAKE OF [I-125] 3,3',5-TRIIODOTHYRONINE (T-3) IN THYROXINE-INDUCED BUT NOT T-3-INDUCED HYPERTHYROID RATS - IMPLICATIONS FOR TRICYCLIC ANTIDEPRESSANT THERAPY
- Creators
- J T GordonE E TomlinsonJ GreenbergM B Dratman
- Publication Details
- The Journal of pharmacology and experimental therapeutics, v 270(1), pp 111-117
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Grant note
- P01MH044210 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) MH45252; MH44210 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Information Science (Informatics)
- Web of Science ID
- WOS:A1994PC02500016
- Scopus ID
- 2-s2.0-0028243886
- Other Identifier
- 991019184018904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy