TY - JOUR
T1 - Molecular targets for the myorelaxant action of diazepam
AU - Crestani, Florence
AU - Löw, Karin
AU - Keist, Ruth
AU - Mandelli, Marie Juliette
AU - Möhler, Hanns
AU - Rudolph, Uwe
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1124/mol.59.3.442
DO - 10.1124/mol.59.3.442
M3 - Article
C2 - 11179437
AN - SCOPUS:0035122824
SN - 0026-895X
VL - 59
SP - 442
EP - 445
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 3
ER -