TY - JOUR
T1 - Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes
AU - Bolden-Watson, C.
AU - Richelson, E.
N1 - Funding Information:
Supported in part by Mayo Foundation and U S P H S grants MH10104 and Pfizer Inc
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
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U2 - 10.1016/0024-3205(93)90194-8
DO - 10.1016/0024-3205(93)90194-8
M3 - Article
C2 - 8445992
AN - SCOPUS:0027475571
SN - 0024-3205
VL - 52
SP - 1023
EP - 1029
JO - Life Sciences
JF - Life Sciences
IS - 12
ER -