Mechanism of action of the hypnotic zolpidem in vivo

Br J Pharmacol. 2000 Dec;131(7):1251-4. doi: 10.1038/sj.bjp.0703717.


Zolpidem is a widely used hypnotic agent acting at the GABA(A) receptor benzodiazepine site. On recombinant receptors, zolpidem displays a high affinity to alpha 1-GABA(A) receptors, an intermediate affinity to alpha(2)- and alpha(3)-GABA(A) receptors and fails to bind to alpha(5)-GABA(A) receptors. However, it is not known which receptor subtype is essential for mediating the sedative-hypnotic action in vivo. Studying alpha1(H101R) mice, which possess zolpidem-insensitive alpha(1)-GABA(A) receptors, we show that the sedative action of zolpidem is exclusively mediated by alpha(1)-GABA(A) receptors. Similarly, the activity of zolpidem against pentylenetetrazole-induced tonic convulsions is also completely mediated by alpha(1)-GABA(A) receptors. These results establish that the sedative-hypnotic and anticonvulsant activities of zolpidem are due to its action on alpha(1)-GABA(A) receptors and not on alpha(2)- or alpha(3)-GABA(A) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Convulsants / pharmacology
  • Diazepam / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • GABA Antagonists / pharmacology
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Motor Activity / drug effects
  • Pentylenetetrazole / pharmacology
  • Pyridines / pharmacology*
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / physiology
  • Zolpidem


  • Anticonvulsants
  • Convulsants
  • GABA Antagonists
  • Hypnotics and Sedatives
  • Pyridines
  • Receptors, GABA-A
  • Zolpidem
  • Diazepam
  • Pentylenetetrazole