Molecular targets for the myorelaxant action of diazepam

Florence Crestani, Karin Löw, Ruth Keist, Marie Juliette Mandelli, Hanns Möhler, Uwe Rudolph

Research output: Contribution to journalArticle

Abstract

Diazepam is used clinically for its myorelaxant, anxiolytic, sedative, and anticonvulsant properties. Although the anxiolytic action is mediated by α2 γ-aminobutyric acid A (GABAA) receptors, the sedative action and in part the anticonvulsant action are mediated by α1 GABAA receptors. To identify the GABAA receptor subtypes mediating the action of diazepam on muscle tone, we have assessed the myorelaxant properties of diazepam in α2(H101R) and α3(H126R) knock-in mice harboring diazepam-insensitive α2 or α3 GABAA receptors, respectively. Whereas in α2(H101R) mice the myorelaxant action of diazepam was almost completely abolished at doses up to 10 mg/kg, the same dose induced myorelaxation in both wild-type and α3(H126R) mice. It was only at a very high dose (30 mg/kg diazepam) that α2(H101R) mice showed partial myorelaxation and α3(H126R) mice were partially protected from myorelaxation compared with wild-type mice. Thus, the myorelaxant activity of diazepam seems to be mediated primarily by α2 GABAA receptors and at high concentrations also by α3 GABAA receptors.

Original languageEnglish (US)
Pages (from-to)442-445
Number of pages4
JournalMolecular Pharmacology
Volume59
Issue number3
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Crestani, F., Löw, K., Keist, R., Mandelli, M. J., Möhler, H., & Rudolph, U. (2001). Molecular targets for the myorelaxant action of diazepam. Molecular Pharmacology, 59(3), 442-445. https://doi.org/10.1124/mol.59.3.442