Abstract

Ten patients with endogenous depression, who had not taken any antidepressive drugs for 3 months, were treated with 100 mg b.i.d. zimelidine (five patients) or 75 mg b.i.d. clomipramine (five patients) for 5-10 weeks. Blood samples taken before and at various times after stopping the treatment were analysed for plasma concentrations of the drugs and their desmethylated metabolites, the uptake of 14C-serotonin in platelets incubated in platelet rich plasma, the concentration of serotonin in whole blood, and the inhibitory effect of the plasma on the accumulation of 14C-serotonin and 3H-noradrenaline in rat hypothalamic synaptosomes. It was found that these uptake measures were normalized within 1 to 2 weeks after zimelidine withdrawal, whereas the effects after clomipramine persisted for 3 to 4 weeks. Norzimelidine, the desmethylated metabolite of zimelidine, caused the effects after zimelidine treatment. Both clomipramine and its metabolite desmethylclomipramine were involved in uptake inhibition after clomipramine treatment. The mean pretreatment values of 14C-serotonin uptake in the platelets did not differ significant from an age and sex matched control group.l

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