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Mechanism of action of the hypnotic zolpidem in vivo
Author(s) -
Crestani Florence,
Martin James R,
Möhler Hanns,
Rudolph Uwe
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703717
Subject(s) - zolpidem , hypnotic , in vivo , mechanism of action , mechanism (biology) , action (physics) , pharmacology , neuroscience , medicine , psychology , chemistry , biology , in vitro , insomnia , philosophy , biochemistry , physics , microbiology and biotechnology , epistemology , quantum mechanics
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 α 2 ‐ and α 3 ‐GABA A receptors and fails to bind to α 5 ‐GABA 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 α 1 ‐GABA A receptors, we show that the sedative action of zolpidem is exclusively mediated by α 1 ‐GABA A receptors. Similarly, the activity of zolpidem against pentylenetetrazole‐induced tonic convulsions is also completely mediated by α 1 ‐GABA A receptors. These results establish that the sedative‐hypnotic and anticonvulsant activities of zolpidem are due to its action on α 1 ‐GABA A receptors and not on α 2 ‐ or α 3 ‐GABA A receptors. British Journal of Pharmacology (2000) 131 , 1251–1254; doi: 10.1038/sj.bjp.0703717