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.
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins; D002997:Clomipramine / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D007099:Imipramine / Q000097:blood*; D007700:Kinetics; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D008875:Middle Aged; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012701:Serotonin / Q000097:blood*
D002352:Carrier Proteins; D003986:Dibenzocycloheptenes; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; C027775:imipramine receptor; C011597:amineptin; D008376:Maprotiline; D012701:Serotonin; D002997:Clomipramine; D007099:Imipramine