Abstract
1. 1. Application of doxepin, an antidepressant with tertiary amine group, in a dose of 60 mg/kg i.p. produced a marked increase in the concentration of rat brain tryptophan and slight, but statistically significant elevation in serotonin (5-HT) concentration. 2. 2. Two hours after the doxepin injection no change in the steady state level of brain 5-hydroxyindoleacetic acid (5-HIAA) was observed. However, in rats treated with pargyline, an inhibitor of monoamine oxidase (MAO), doxepin retarded 5-HIAA decline. Moreover, in rats receiving probenecid, a drug that blocks elimination of acidic metabolites from central nervous system (CNS), doxepin decelerated the rate of 5-HIAA accumulation. 3. 3. In vitro doxepin inhibited the uptake of 5-HT into human blood platelets. 4. 4. Our data indicate, that doxepin exerts its effect on brain serotoninergic neurons by same or similar mechanisms as the other tricyclic antidepressants with tertiary amine in side chain, i.e. by inhibition of 5-HT reuptake mechanism.
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