The GABA(A) receptor antagonist picrotoxin inhibits 5-hydroxytryptamine type 3A receptors

Neuropharmacology. 2003 Mar;44(4):431-8. doi: 10.1016/s0028-3908(03)00032-7.


For a number of years it has been known that the CNS convulsant picrotoxin inhibits the GABA(A) receptor, an anion-selective member of the ligand-gated ion channel (LGIC) superfamily. PTX also inhibits other anion-selective LGIC members, such as GABA(C), glycine and glutamate-gated Cl(-) channels. In the present report, we tested the ability of picrotoxin to inhibit cation-selective 5-HT(3A) receptors. Murine 5-HT(3A) receptors were expressed in HEK293 cells, and functionally evaluated using whole-cell patch clamp recording. Picrotoxin inhibited 5-HT-gated currents in a concentration-dependent manner, with an IC(50) of approximately 30 microM. Moreover, the blockade by PTX was non-competitive and use-facilitated. Pentylenetetrazole and U-93631, ligands that act at a domain similar to that of picrotoxin in GABA(A) receptors, also inhibited the 5-HT(3A) receptor. For each ligand tested, its potency was 5-10 fold lower than typically observed in GABA(A) receptors. Our results demonstrate that, in addition to being a relatively non-selective inhibitor of anionic LGICs, picrotoxin also inhibits the cation-selective 5-HT(3A) receptor. Moreover, the fact that both PTZ and U-93631 similarly inhibit the 5-HT(3A) receptor is consistent with the suggestion that the site of picrotoxin action in this receptor may be comparable to that in anion-selective LGICs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • GABA Antagonists / pharmacology*
  • GABA-A Receptor Antagonists*
  • Humans
  • Ligands
  • Mice
  • Pentylenetetrazole / pharmacology
  • Picrotoxin / pharmacology*
  • Quinoxalines / pharmacology
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / pharmacology*


  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Ligands
  • Quinoxalines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Picrotoxin
  • U 93631
  • Pentylenetetrazole