Evidence for a possible role of 5-hydroxytryptamine in the genesis of fatigue in man: administration of paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise

Exp Physiol. 1992 Nov;77(6):921-4. doi: 10.1113/expphysiol.1992.sp003660.


Seven healthy subjects exercised to exhaustion on a bicycle ergometer at a power output corresponding to 70% of maximum oxygen uptake after administration of either a placebo or 20 mg of paroxetine, a serotonin re-uptake inhibitor. Exercise time after paroxetine (median 94 min; range 84-127 min) was less (P < 0.05) than after placebo (median 116 min; range 86-133 min). The metabolic and cardiorespiratory responses to exercise were the same in both trials. This result supports the suggestion that there is a central component to fatigue which is mediated by the activity of serotoninergic neurones.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Exercise Test
  • Fatigue / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Oxygen Consumption
  • Paroxetine / pharmacology*
  • Physical Endurance / drug effects*
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology*
  • Time Factors


  • Serotonin Antagonists
  • Serotonin
  • Paroxetine