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.
D000662:Amphetamines / Q000037:antagonists & inhibitors*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005473:Fluoxetine / Q000031:analogs & derivatives; D006892:Hydroxydopamines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010647:Phenyl Ethers / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity
D000662:Amphetamines; D000929:Antidepressive Agents, Tricyclic; D006892:Hydroxydopamines; D010647:Phenyl Ethers; D011437:Propylamines; D005473:Fluoxetine; C011386:nisoxetine; D012701:Serotonin; D010133:p-Chloroamphetamine; D009638:Norepinephrine