γ amino-butyric acid type-A receptors (GABARs) containing γ2 or δ subunits form separate pools of receptors in vivo, with distinct localization and function. We determined the rate of surface membrane...

Chronic pain is an unwelcome consequence of inflammatory disease and nerve injury that currently has no effective treatment. This paper shows that specific pharmacological inhibition of α2 and α3 subu...

Read the full paper: Phospholipid flippases ATP8A1 and ATP8A2 regulate GABAA receptor trafficking through distinct mechanisms in hippocampal neurons

Achalasia is a rare esophageal motility disorder of poorly understood etiology. Here, we perform a large trio-based whole-genome sequencing study of achalasia and identify a recessively inherited frameshift variant in FAM129C (p.Ala454fs). A CRISPR/Cas9-engineered Fam129c-mutant mouse model recapitulating key features of achalasia was established, including growth retardation, elevated lower esophageal sphincter (LES) pressure, and selective loss of inhibitory neurons. Multi-omic analyses revealed substantial B cell expansion and activation within the LES, accompanied by enhanced humoral immune responses. Time-course experiments demonstrated that B cell accumulation preceded overt neuronal loss, while B cell depletion via anti-CD20 antibodies or intravenous immunoglobulin treatment partially rescued the phenotypes. Further protein profiling and cell-based assays suggested that the GABAA receptor may represent one potential neuronal antigen targeted by circulating autoantibodies. Togeth

Designer benzodiazepines (DBZDs) are a class of new psychoactive substances (NPS) designed as legal alternatives to prescription BZDs. Bromazolam has been the most prevalent DBZD detected on the recreational market around the world; however, a new DBZD, ethylbromazolam (8-bromo-1-ethyl-6-phenyl-4 H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine; also known as bromoethylazolam) has recently emerged. In this study, the emergence of ethylbromazolam in Canada, the UK, and Australia is reported based on analysis of samples from drug checking services and in Germany based on analysis of samples seized by customs and mail services. Since November 2024, ethylbromazolam has been increasingly detected with a concurrent decrease in bromazolam detections, suggesting that its emergence is likely in response to the international control of bromazolam on 3rd December 2024. Additionally, increased detections of other DBZDs, including desalkylgidazepam (bromonordiazepam) and clobromazolam (phenazolam) have

Paradoxically, mutations that enhance GABAA receptor function cause severe epilepsy. Using a mouse model of a human gain-of-function GABAA receptor mutatio

Paradoxically, mutations that enhance GABAA receptor function cause severe epilepsy. Using a mouse model of a human gain-of-function GABAA receptor mutatio

Benzodiazepines contribute to numerous drug-related deaths and designer benzodiazepines (DBZDs) with limited pharmacodynamic data available have been increasingly implicated. Here, the authors use an in vitro GABAA assay to reveal that most DBZDs are positive allosteric modulators with wide variation in potency and efficacy, providing crucial insights for intoxication interpretation, harm reduction, and legislative measures.

Communications Chemistry, Published online: 07 April 2026; doi:10.1038/s42004-026-02001-xBenzodiazepines contribute to numerous drug-related deaths and designer benzodiazepines (DBZDs) with limited pharmacodynamic data available have been increasingly implicated. Here, the authors use an in vitro GABAA assay to reveal that most DBZDs are positive allosteric modulators with wide variation in potency and efficacy, providing crucial insights for intoxication interpretation, harm reduction, and legislative measures.