| Title | Mechanism of action of the hypnotic zolpidem in vivo. | | Author(s) | Crestani F, Martin JR, Möhler H, Rudolph U | | Institution | Institute of Pharmacology and Toxicology, University of Zurich, Switzerland. crestani@pharma.unizh.ch | | Source | Br J Pharmacol 2000 Dec; 131(7):1251-4. | | MeSH | Animals
Anticonvulsants
Convulsants
Diazepam
Dose-Response Relationship, Drug
Female
GABA Antagonists
Hypnotics and Sedatives
Male
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Motor Activity
Pentylenetetrazole
Pyridines
Receptors, GABA-A
Research Support, Non-U.S. Gov't
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11090095 |
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