Changes in [3H]5-HT uptake and [3H]imipramine binding in platelets after chlorimipramine in healthy volunteers. Comparison with maprotiline and amineptine.

In the platelets of normal healthy volunteers (n = 8) taking chlorimipramine (50 mg/day) for 1 week, the saturable uptake of [3H]5-hydroxytryptamine (5-HT) was fully inhibited at the end of the week, but returned to control values after 2 weeks washout. The Bmax of [3H]imipramine binding was decreased by 63% at the end of the treatment and remained significantly decreased below control values after 1 week washout, whereas the Kd values were increased at the end of the treatment, but had returned to baseline values after 1 week washout. The time course of recovery following the administration of chlorimipramine showed some variation between subjects, but it was necessary to wait up to 4 weeks of washout before the Bmax of [3H]imipramine returned to baseline levels. In contrast, neither 1-week treatment with maprotiline (50 mg/day) nor with amineptine (100 mg/day) changed the parameters of [3H]5-HT uptake or [3H]imipramine binding in platelets from healthy volunteers. These results support the following conclusions. (1) [3H]Imipramine binding in platelets can be down-regulated by relatively low, subtherapeutic doses of chlorimipramine. (2) It is possible to dissociate [3H]imipramine binding parameters from [3H]5-HT uptake because the time course of recovery was clearly different, indicating that [3H]imipramine labels a site linked with, but different from, the 5-HT recognition site in the transporter complex. (3) A washout of antidepressants of 4 weeks may be needed when studying the parameters of [3H]imipramine binding in platelets from depressed patients if the previous medication involved chlorimipramine. For antidepressants like maprotiline or amineptine, that act through mechanisms other than inhibition of 5-HT uptake, the time of washout appears to be less critical, although it is not possible to rule out the existence of some secondary modifications influencing the 5-HT transporter complex.