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Behavioural and neurochemical proteins of 1-[1-([indol-3-yl] methyl) piperid-4-yl]-3-benzoylurea (Wy 25093) in rodents.

Wy 25093 is a novel, selective and potent inhibitor of the neuronal 5-hydroxytryptamine (5-HT) uptake process in vitro and in vivo. The compound was more potent than clomipramine and fluoxetine as an inhibitor of 5-HT uptake in vitro and did not significantly inhibit catecholamine uptake. In addition, Wy 25093 potentiated the behavioural syndrome induced by 5-hydroxytryptophan (5-HTP) and antagonised the hyperactivity produced by p-chloroamphetamine (P-CA). WY 25093 antagonised the (P-CA)-induced depletion of 5-HT in rat brain and reduced the probenecid-induced increase in rat brain 5-hydroxyindole-3-acetic acid (5-HIAA). Acute administration of the agent to rats resulted in reduced 5-HIAA levels without affecting 5-HT; chronic treatment with the compound produced decreases in the levels of both 5-HIAA and 5-HT. It is concluded that Wy 25093 is a selective and potent inhibitor of the neuronal re-uptake process for 5-HT both in vitro and in vivo, and may possess potential antidepressant activity.