Inhibition and dissociation of [3H]-paroxetine binding to human platelets.

Previous data on dissociation studies of [3H]-imipramine and [3H]-paroxetine binding to the human platelet 5-hydroxytryptamine (5-HT, serotonin) transporter have suggested that the binding is heterogeneous in nature and/or is subject to allosteric modifications through a separate low affinity site. The platelet 5-HT transporter is often used as a biological marker in psychiatric conditions. Therefore, it was of interest to further characterize the 5-HT uptake site by using [3H]-paroxetine. The 5-HT uptake inhibitors tested (citalopram, clomipramine, imipramine, norzimeldine and paroxetine) and 5-HT itself produced competitive inhibition patterns in saturation experiments, suggesting that these agents bind to the same site. In dissociation experiments in the presence of the 5-HT uptake inhibitors, the half-time values for dissociation were the same, whereas 5-HT slowed the dissociation. These data suggest that with the concentrations used of the 5-HT uptake inhibitors, they do not modify the 5-HT transporter. However, in the presence of 5-HT, the [3H]-paroxetine dissociation is decreased, suggesting an allosteric modification of the [3H]-paroxetine binding site.