Fluoxetine enantiomers as antagonists of p-chloroamphetamine effects in rats

Pharmacol Biochem Behav. 1986 Feb;24(2):281-4. doi: 10.1016/0091-3057(86)90351-5.


The dextrorotatory enantiomer of fluoxetine was slightly more potent than the levorotatory enantiomer in antagonizing the depletion of brain serotonin by p-chloroamphetamine in rats. The time course of the depletion of brain serotonin at times out to 24 hr after the injection of p-chloroamphetamine was determined with or without simultaneous administration of one of the fluoxetine enantiomers. The dextrorotatory enantiomer prevented the depletion of brain serotonin at any time after p-chloroamphetamine. The levorotatory enantiomer prevented the initial depletion of brain serotonin at 2 and 4 hr, but by 8 hr brain serotonin concentration was decreased and by 24 hr the depletion of serotonin was almost as great as in rats treated with p-chloroamphetamine alone. The elevation of serum corticosterone that occurred acutely after injection of a low dose of p-chloroamphetamine was significantly antagonized by both enantiomers of fluoxetine, the dextrorotatory enantiomer being slightly more potent. In contrast, the lowering of DOPAC (3,4-dihydroxyphenylacetic acid) concentration in rat brain by p-chloroamphetamine was not antagonized by either enantiomer of fluoxetine, indicating this effect is not secondary to serotonin release by p-chloroamphetamine. The results are consistent with other evidence that both enantiomers of fluoxetine are potent inhibitors of serotonin uptake, the dextrorotatory enantiomer being longer-acting than the levorotatory enantiomer in rats.

MeSH terms

  • Amphetamines / antagonists & inhibitors*
  • Animals
  • Brain Chemistry / drug effects
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacology*
  • Male
  • Propylamines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Stereoisomerism
  • Time Factors
  • p-Chloroamphetamine / antagonists & inhibitors*


  • Amphetamines
  • Propylamines
  • Fluoxetine
  • Serotonin
  • p-Chloroamphetamine