Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-SelectiveGABAA Receptor Modulators?
Joint Authors
Vinkers, Christiaan H.
Olivier, Berend
Source
Advances in Pharmacological and Pharmaceutical Sciences
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-19, 19 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-03-29
Country of Publication
Egypt
No. of Pages
19
Main Subjects
Abstract EN
Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete.
In appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all.
In light of this evidence, we review the current evidence for the neuroadaptive mechanisms underlying benzodiazepine tolerance, including changes of (i) the GABAA receptor (subunit expression and receptor coupling), (ii) intracellular changes stemming from transcriptional and neurotrophic factors, (iii) ionotropic glutamate receptors, (iv) other neurotransmitters (serotonin, dopamine, and acetylcholine systems), and (v) the neurosteroid system.
From the large variance in the studies, it appears that either different (simultaneous) tolerance mechanisms occur depending on the benzodiazepine effect, or that the tolerance-inducing mechanism depends on the activated GABAA receptor subtypes.
Importantly, there is no convincing evidence that tolerance occurs with α subunit subtype-selective compounds acting at the benzodiazepine site.
American Psychological Association (APA)
Vinkers, Christiaan H.& Olivier, Berend. 2012. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-SelectiveGABAA Receptor Modulators?. Advances in Pharmacological and Pharmaceutical Sciences،Vol. 2012, no. 2012, pp.1-19.
https://search.emarefa.net/detail/BIM-991426
Modern Language Association (MLA)
Vinkers, Christiaan H.& Olivier, Berend. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-SelectiveGABAA Receptor Modulators?. Advances in Pharmacological and Pharmaceutical Sciences No. 2012 (2012), pp.1-19.
https://search.emarefa.net/detail/BIM-991426
American Medical Association (AMA)
Vinkers, Christiaan H.& Olivier, Berend. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-SelectiveGABAA Receptor Modulators?. Advances in Pharmacological and Pharmaceutical Sciences. 2012. Vol. 2012, no. 2012, pp.1-19.
https://search.emarefa.net/detail/BIM-991426
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-991426