Abstract
Administration of imipramine, 30 mg/kg, i.p., to rats decreased 5-HIAA and increased 5-HT in the brain. The increase in brain 5-HT was inconsistent. Imipramine inhibited the accumulation of 5-HIAA in rat brain after pretreatment with probenecid. Administration of 1-tryptophan (1-TP) to imipramine-pretreated rats resulted in an increase in brain 5-HT which was significantly lower than controls. When 1-5-hydroxytryptophan was given instead of 1-TP, the formation of brain 5-HT was not decreased but showed a tendency to be increased. After the administration of 1-TP, the rise in plasma TP was higher in imipramine pretreated rats than in controls. Uptake of 1-TP by a crude synaptosomal fraction in vitro showed that imipramine inhibited the uptake of 1-TP competitively. It is concluded that imipramine might inhibit the biosynthesis of 5-HT by inhibiting the uptake of TP.
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