Lack of binding of acetaminophen to 5-HT receptor or uptake sites (or eleven other binding/uptake assays)

Life Sci. 1996;59(2):PL37-40. doi: 10.1016/0024-3205(96)00273-1.


The mechanism of analgesic action of acetaminophen (paracetamol) remains unknown. However, a central component distinct from that of the NSAIDs (non-steroidal antiinflammatory drugs) seems likely. A recent report (NeuroReport 6:1546-1548, 1995) suggests the involvement of 5-HT3 receptors. In the present study, we measured the affinity of acetaminophen at 5-HT3, as well as 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2, 5-HT2C, 5-HT4, 5-HT6, 5-HT7 and eleven other receptor sites and at serotonin and norepinephrine reuptake sites. At 10 microM, acetaminophen inhibited less than 10% specific radioligand binding at any site. These findings: (i) suggest that acetaminophen's effect on serotonergic pathways is indirect, and (ii) circumscribe acetaminophen's possible central analgesic mechanism(s).

MeSH terms

  • Acetaminophen / pharmacology*
  • Animals
  • Binding, Competitive
  • Cattle
  • Cerebral Cortex / drug effects
  • Guinea Pigs
  • Heart / drug effects
  • Rats
  • Receptors, Serotonin / drug effects*
  • Swine


  • Receptors, Serotonin
  • Acetaminophen