Mechanism of action of the hypnotic zolpidem in vivo

Mechanism of action of the hypnotic zolpidem in vivo Zolpidem is a widely used hypnotic agent acting at the GABAA receptor benzodiazepine site. On recombinant receptors, zolpidem displays a high affinity to α1‐GABAA receptors, an intermediate affinity to α2‐ and α3‐GABAA receptors and fails to bind to α5‐GABAA 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‐GABAA receptors, we show that the sedative action of zolpidem is exclusively mediated by α1‐GABAA receptors. Similarly, the activity of zolpidem against pentylenetetrazole‐induced tonic convulsions is also completely mediated by α1‐GABAA receptors. These results establish that the sedative‐hypnotic and anticonvulsant activities of zolpidem are due to its action on α1‐GABAA receptors and not on α2‐ or α3‐GABAA receptors. British Journal of Pharmacology (2000) 131, 1251–1254; doi:10.1038/sj.bjp.0703717 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Mechanism of action of the hypnotic zolpidem in vivo

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Publisher
Wiley
Copyright
2000 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0703717
pmid
11090095
Publisher site
See Article on Publisher Site

Abstract

Zolpidem is a widely used hypnotic agent acting at the GABAA receptor benzodiazepine site. On recombinant receptors, zolpidem displays a high affinity to α1‐GABAA receptors, an intermediate affinity to α2‐ and α3‐GABAA receptors and fails to bind to α5‐GABAA 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‐GABAA receptors, we show that the sedative action of zolpidem is exclusively mediated by α1‐GABAA receptors. Similarly, the activity of zolpidem against pentylenetetrazole‐induced tonic convulsions is also completely mediated by α1‐GABAA receptors. These results establish that the sedative‐hypnotic and anticonvulsant activities of zolpidem are due to its action on α1‐GABAA receptors and not on α2‐ or α3‐GABAA receptors. British Journal of Pharmacology (2000) 131, 1251–1254; doi:10.1038/sj.bjp.0703717

Journal

British Journal of PharmacologyWiley

Published: Dec 1, 2000

References

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