Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype
نویسندگان
چکیده
منابع مشابه
Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype
Agonists at the benzodiazepine-binding site of GABAA receptors (BDZs) enhance synaptic inhibition through four subtypes (α1, α2, α3 and α5) of GABAA receptors (GABAAR). When applied to the spinal cord, they alleviate pathological pain; however, insufficient efficacy after systemic administration and undesired effects preclude their use in routine pain therapy. Previous work suggested that subty...
متن کاملDifferent residues in the GABAA receptor benzodiazepine binding pocket mediate benzodiazepine efficacy and binding.
Benzodiazepines (BZDs) exert their therapeutic actions by binding to the GABA(A) receptor (GABA(A)R) and allosterically modulating GABA-induced chloride currents (I(GABA)). A variety of ligands with divergent structures bind to the BZD site, and the structural mechanisms that couple their binding to potentiation of I(GABA) are not well understood. In this study, we measured the effects of indiv...
متن کاملMechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABAA Receptor Modulators?
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 ...
متن کاملContext Dependent Benzodiazepine Modulation of GABAA Receptor Opening Frequency
The anxiolytic, hypnotic, and anti-convulsant properties of benzodiazepines (BDZs) require modulation of distinct GABA(A) receptor alpha-subtypes. BDZ modulation of GABA(A) receptors is often described in terms of increased opening frequency, and contrasted with the increased open durations occurring with barbiturate modulation. Several studies spanning single channel, rapid kinetic, and whole ...
متن کاملGABA antagonists differentiate between recombinant GABAA/benzodiazepine receptor subtypes.
Seventeen rat GABAA receptor subtypes were transiently expressed in the human embryonic kidney 293 cell line from alpha 1, alpha 2, alpha 3, alpha 5, or alpha 6 variants with any of the three beta subunits and gamma 2S or gamma 3. We obtained fingerprints in the form of subtype characteristic concentration-response curves of 35S-TBPS binding to GABA and the GABAA antagonists SR 95531 and bicucu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Nature Communications
سال: 2015
ISSN: 2041-1723
DOI: 10.1038/ncomms7803