MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Crestani, F.
Right arrow Articles by Rudolph, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Crestani, F.
Right arrow Articles by Rudolph, U.

Vol. 59, Issue 3, 442-445, March 2001

ACCELERATED COMMUNICATION
Molecular Targets for the Myorelaxant Action of Diazepam

Florence Crestani, Karin Löw,1 Ruth Keist, Marie-Juliette Mandelli,2 Hanns Möhler, and Uwe Rudolph

Institute of Pharmacology and Toxicology, University of Zürich and Swiss Federal Institute of Technology Zürich (ETHZ), Zürich, Switzerland

Diazepam is used clinically for its myorelaxant, anxiolytic, sedative, and anticonvulsant properties. Although the anxiolytic action is mediated by alpha 2 gamma -aminobutyric acid A (GABAA) receptors, the sedative action and in part the anticonvulsant action are mediated by alpha 1 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 alpha 2(H101R) and alpha 3(H126R) knock-in mice harboring diazepam-insensitive alpha 2 or alpha 3 GABAA receptors, respectively. Whereas in alpha 2(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 alpha 3(H126R) mice. It was only at a very high dose (30 mg/kg diazepam) that alpha 2(H101R) mice showed partial myorelaxation and alpha 3(H126R) mice were partially protected from myorelaxation compared with wild-type mice. Thus, the myorelaxant activity of diazepam seems to be mediated primarily by alpha 2 GABAA receptors and at high concentrations also by alpha 3 GABAA receptors.

1 Present address: Department of Neurosciences, University of California, San Diego, La Jolla, California.

2 Present address: Department of Neurology, Vestibulo-Ocular Laboratory, University Hospital, Zürich, Switzerland.

Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
A. Zeller, F. Crestani, I. Camenisch, T. Iwasato, S. Itohara, J. M. Fritschy, and U. Rudolph
Cortical Glutamatergic Neurons Mediate the Motor Sedative Action of Diazepam
Mol. Pharmacol., February 1, 2008; 73(2): 282 - 291.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. C. Licata, D. M. Platt, J. M. Cook, P. V. V. S. Sarma, G. Griebel, and J. K. Rowlett
Contribution of GABAA Receptor Subtypes to the Anxiolytic-Like, Motor, and Discriminative Stimulus Effects of Benzodiazepines: Studies with the Functionally Selective Ligand SL651498 [6-Fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyridol[3,4-b]indol-1-one]
J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1118 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. K. Rowlett, D. M. Platt, S. Lelas, J. R. Atack, and G. R. Dawson
Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates
PNAS, January 18, 2005; 102(3): 915 - 920.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. van Rijnsoever, M. Tauber, M. K. Choulli, R. Keist, U. Rudolph, H. Mohler, J. M. Fritschy, and F. Crestani
Requirement of {alpha}5-GABAA Receptors for the Development of Tolerance to the Sedative Action of Diazepam in Mice
J. Neurosci., July 28, 2004; 24(30): 6785 - 6790.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Kopp, U. Rudolph, K. Low, and I. Tobler
Modulation of rhythmic brain activity by diazepam: GABAAreceptor subtype and state specificity
PNAS, March 9, 2004; 101(10): 3674 - 3679.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
G. S. Findlay, R. Phelan, M. T. Roberts, G. E. Homanics, S. E. Bergeson, G. F. Lopreato, S. J. Mihic, Y. A. Blednov, and R. A. Harris
Glycine Receptor Knock-In Mice and Hyperekplexia-Like Phenotypes: Comparisons with the Null Mutant
J. Neurosci., September 3, 2003; 23(22): 8051 - 8059.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Crestani, R. Keist, J.-M. Fritschy, D. Benke, K. Vogt, L. Prut, H. Bluthmann, H. Mohler, and U. Rudolph
Trace fear conditioning involves hippocampal alpha 5 GABAA receptors
PNAS, June 25, 2002; 99(13): 8980 - 8985.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. S. Findlay, M. J. Wick, M. P. Mascia, D. Wallace, G. W. Miller, R. A. Harris, and Y. A. Blednov
Transgenic Expression of a Mutant Glycine Receptor Decreases Alcohol Sensitivity of Mice
J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 526 - 534.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Mohler, J. M. Fritschy, and U. Rudolph
A New Benzodiazepine Pharmacology
J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 2 - 8.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics