Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes

C. Bolden-Watson, E. Richelson

Research output: Contribution to journalArticle

396 Citations (Scopus)

Abstract

We determined the uptake blockade produced by eight new antidepressant drugs (etoperidone, femoxetine, lofepramine, nefazodone, paroxetine, sertraline, tomoxetine, and venlafaxine), two metabolites of newer antidepressants (desmethylsertraline and norfluoxetine), seven previously reported antidepressants, and carbamazepine. Inhibitor constants (Kis) for uptake blockade were obtained from competitive uptake studies with [3H]norepinephrine, [3H]5-hydroxytryptamine, and [3H]dopamine in rat brain synaptosomes prepared from hippocampus, frontal cortex, and striatum, respectively. Among the newer compounds, tomoxetine (Ki = 0.7 nM) and lofepramine (Ki = 1.9 nM) were potent and selective [3H]norepinephrine uptake blockers; paroxetine (Ki = 0.73 nM), sertraline (Ki = 3.4 nM), and femoxetine (Ki = 22 nM) potently and selectively inhibited [3H]5-hydroxytryptamine uptake. Although none of the drugs was potent for [3H]dopamine uptake blockade, sertraline was the most potent (Ki=260 nM). These data are useful in predicting adverse effects and drug-drug interactions of antidepressants.

Original languageEnglish (US)
Pages (from-to)1023-1029
Number of pages7
JournalLife Sciences
Volume52
Issue number12
DOIs
StatePublished - 1993

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Biogenic Amines
Synaptosomes
Sertraline
Antidepressive Agents
Rats
Lofepramine
Brain
Paroxetine
Dopamine
Serotonin
Norepinephrine
Drug interactions
Carbamazepine
Frontal Lobe
Metabolites
Drug Interactions
Pharmaceutical Preparations
Hippocampus
femoxetine
Atomoxetine Hydrochloride

ASJC Scopus subject areas

  • Pharmacology

Cite this

Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. / Bolden-Watson, C.; Richelson, E.

In: Life Sciences, Vol. 52, No. 12, 1993, p. 1023-1029.

Research output: Contribution to journalArticle

Bolden-Watson, C. ; Richelson, E. / Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. In: Life Sciences. 1993 ; Vol. 52, No. 12. pp. 1023-1029.
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