2012/01/01 by Christiaan H. Vinkers, Berend Olivier · 1 citation
Neuroscience · Biochemistry, Genetics and Molecular Biology · Medicine · #Neuroscience and Neuropharmacology Research #Memory and Neural Mechanisms #Receptor Mechanisms and Signaling #Neuroscience #GABAA receptor #Pharmacology #Benzodiazepine #Zolpidem #Ionotropic effect #Anxiolytic #Medicine #Receptor #Glutamate receptor #Biology #Internal medicine
paper · pdf · doi:10.1155/2012/416864
openalex publication_date 2012/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/29
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 GABA(A) 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 GABA(A) receptor subtypes. Importantly, there is no convincing evidence that tolerance occurs with α subunit subtype-selective compounds acting at the benzodiazepine site.