The comparison of fluoxetine and nisoxetine with tricyclic antidepressants in blocking the neurotoxicity of p-chloroamphetamine and 6-hydroxydopamine in the rat brain.

Fluoxetine prevents the loss of 5-hydroxytryptamine (5HT) uptake in synaptosomes of cerebral cortex after intraperitoneally administered p-chloroamphetamine (p-CA) with an ED50 of 3.8 mg/kg i.p. in rats. However, at 50 mg/kg, it does not prevent the loss of norepinephrine (NE) uptake in synaptosomes of hypothalamus after intraventricularly administered 6-hydroxydopamine (6-OHDA). Nisoxetine, on the other hand, centrally protects NE uptake from the neurotoxic effect of 6-OHDA with an ED50 value of 5 mg/kg i.p. At 50 mg/kg, it gives only 35% protection of 5HT uptake from the neurotoxic effect of p-CA. In comparison with the ED50 values of tricyclic antidepressants, both fluoxetine and nisoxetine are more potent and selective blockers of neurotoxicity resulting from the central actions of p-CA and 6-OHDA, respectively, in vivo.