1. Changes in [3H]5-HT uptake and [3H]imipramine binding in platelets after chlorimipramine in healthy volunteers. Comparison with maprotiline and amineptine.
- Author
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Poirier MF, Galzin AM, Loo H, Pimoule C, Segonzac A, Benkelfat C, Sechter D, Zarifian E, Schoemaker H, and Langer SZ
- Subjects
- Adult, Blood Platelets metabolism, Dibenzocycloheptenes pharmacology, Female, Humans, Kinetics, Male, Maprotiline pharmacology, Middle Aged, Receptors, Neurotransmitter drug effects, Blood Platelets drug effects, Carrier Proteins, Clomipramine pharmacology, Imipramine blood, Receptors, Drug, Serotonin blood
- Abstract
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.
- Published
- 1987
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