Inhibition of sodium-dependent [3H]imipramine binding in rat brain by serotonin and serotonin uptake inhibitors.
The sodium-dependent component of [3H]imipramine binding in rat cerebral cortex was completely displaced by serotonin and non-tricyclic (fluoxetine) as well as tricyclic (clomipramine) serotonin uptake inhibitors. The competition curves were monophasic yielding pseudo-Hill coefficient close to unity and IC50 values of 89, 10 and 6 nM, respectively for serotonin, fluoxetine and clomipramine. The Ki of serotonin for the sodium-dependent [3H]imipramine binding was within the range of its Km for the uptake process. These results suggest that sodium-dependent [3H]imipramine sites relevant for serotonin uptake may be the same as the substrate recognition sites on the serotonin transporter.
Hrdina
P D
PD
Department of Pharmacology, School of Medicine, University of Ottawa, Canada.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002997:Clomipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D014196:Trazodone / Q000494:pharmacology
D011985:Receptors, Serotonin; D005473:Fluoxetine; D012701:Serotonin; D012964:Sodium; D002997:Clomipramine; D007099:Imipramine; D014196:Trazodone