Kinetics of the interaction of sertraline with the human platelet plasma membrane 5-hydroxytryptamine carrier.
Sertraline, a new selective 5-HT uptake inhibitor showed a mixed pattern of inhibition of human platelet 5-HT uptake with a Ki value of 2.5 nM and K'i value of 25 nM. Imipramine and alaproclate were found to be fully competitive inhibitors of 5-HT uptake with Ki values of 8 and 130 nM respectively. Sertraline was a fully competitive inhibitor of high-affinity [3H]imipramine binding to platelet membranes with a Ki value of 1.3 nM, as was alaproclate and 5-HT with Ki values of 170 and 800 nM respectively. Both sertraline and imipramine, at a concentration of 10 microM caused a fast monophasic dissociation of [3H]imipramine from platelet membranes in contrast to serotonin which caused a slow monophasic dissociation.
Phillips
O M
OM
Department of Biochemistry, Trinity College, Dublin, Ireland.
Wood
K M
KM
Williams
D C
DC
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000097:blood*; D020280:Sertraline
D009281:Naphthalenes; D011985:Receptors, Serotonin; D012701:Serotonin; D015057:1-Naphthylamine; C025293:alaproclate; D000409:Alanine; D007099:Imipramine; D020280:Sertraline