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 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 language | English (US) |
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Pages (from-to) | 1251-1254 |
Number of pages | 4 |
Journal | British Journal of Pharmacology |
Volume | 131 |
Issue number | 7 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Benzodiazepines
- GABA(A) receptor
- Knock-in mouse
- Targeted mutation
- Zolpidem
ASJC Scopus subject areas
- Pharmacology