Mechanism of action of the hypnotic zolpidem in vivo

Florence Crestani, James R. Martin, Hanns Möhler, Uwe Rudolph

Research output: Contribution to journalArticlepeer-review


Zolpidem is a widely used hypnotic agent acting at the GABA(A) receptor benzodiazepine site. On recombinant receptors, zolpidem displays a high affinity to α1-GABA(A) receptors, an intermediate affinity to α2- and α3-GABA(A) receptors and fails to bind to α5GABA(A) receptors. However, it is not known which receptor subtype is essential for mediating the sedative-hypnotic action in vivo. Studying α1(H101R) mice, which possess zolpidem-insensitive α1-GABA(A) receptors, we show that the sedative action of zolpidem is exclusively mediated by α1-GABA(A) receptors. Similarly, the activity of zolpidem against pentylenetetrazole-induced tonic convulsions is also completely mediated by α1-GABA(A) receptors. These results establish that the sedative-hypnotic and anticonvulsant activities of zolpidem are due to its action on α1-GABA(A) receptors and not on α2 or α3GABA(A) receptors.

Original languageEnglish (US)
Pages (from-to)1251-1254
Number of pages4
JournalBritish Journal of Pharmacology
Issue number7
StatePublished - 2000
Externally publishedYes


  • Benzodiazepines
  • GABA(A) receptor
  • Knock-in mouse
  • Targeted mutation
  • Zolpidem

ASJC Scopus subject areas

  • Pharmacology


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