Selective labeling of serotonin uptake sites in rat brain by [3H]citalopram contrasted to labeling of multiple sites by [3H]imipramine.
Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes [3H]citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for [3H]citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of [3H]citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of [3H]citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of [3H]imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific [3H]imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of [3H]imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in [3H]citalopram and serotonin-sensitive [3H]imipramine binding with only a small effect on serotonin-insensitive [3H]imipramine binding. The dissociation rate of [3H]imipramine or [3H]citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive [3H]imipramine high affinity binding sites closely resembles that of [3H]citalopram binding.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015283:Citalopram; D007099:Imipramine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011437:Propylamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution; D014316:Tritium; D010133:p-Chloroamphetamine / Q000494:pharmacology
D011437:Propylamines; D011985:Receptors, Serotonin; D015283:Citalopram; D014316:Tritium; D012701:Serotonin; D010133:p-Chloroamphetamine; D007099:Imipramine