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

C. Bolden-Watson, E. Richelson

Research output: Contribution to journalArticlepeer-review

400 Scopus citations


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
Issue number12
StatePublished - 1993

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology


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