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  • Title: From clomipramine to mianserin: therapeutic relevance of interactions with serotonin uptake and storage, as studied in the blood platelet model.
    Author: Lingjaerde O.
    Journal: Acta Psychiatr Scand Suppl; 1985; 320():10-9. PubMed ID: 3901671.
    Abstract:
    Inhibition of active serotonin uptake into neurones and platelets is a common effect of tricyclic and related antidepressants, and has been regarded as one of the more important mechanisms of action of such drugs. However, as is shown in this survey, the antidepressants vary widely in their potency as inhibitors of platelet serotonin uptake, and they also differ in the type of inhibition kinetics, from purely competitive to mixed competitive/noncompetitive. The therapeutic relevance of this effect is discussed. Serotonin uptake inhibition seems to be one of several mechanisms for obtaining the required normalization of monoamine dysfunction in depression. Analysis of efflux from platelets preloaded with a moderate amount of 14C-serotonin provides information on the storage and compartmentation of serotonin in the platelets, and on the rate of efflux from the different compartments. When present during the preloading phase, some antidepressants seem to produce a relative increase in serotonin in the granular storage compartment when compared to the smaller cytoplasmic compartment. This effect is in some respects opposite to that exerted by reserpine, and possibly may be pharmacologically relevant.
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