Last update 01 Nov 2024

GABAB receptor x GABAA receptor

Last update 01 Nov 2024

Basic Info

Related Targets

GABAB receptorGABAA receptor

Drugs associated with GABAB receptor x GABAA receptor

CGP-46381

Target

GABAA receptor x GABAB receptor

Mechanism

GABAA receptor antagonists [+1]

Active Org.

Institute of Physics AS CR

Originator Org.

Ciba-Geigy AG

Active Indication

Epilepsy

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GABAB receptor x GABAA receptor

100 Translational Medicine associated with GABAB receptor x GABAA receptor

0 Patents (Medical) associated with GABAB receptor x GABAA receptor

369

Literatures (Medical) associated with GABAB receptor x GABAA receptor

11 Jun 2024·Proceedings of the National Academy of Sciences

Developmental hearing loss–induced perceptual deficits are rescued by genetic restoration of cortical inhibition

Article

Author: Fair, Regan ; Mowery, Todd M. ; Masri, Samer ; Sanes, Dan H.

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss–induced perceptual deficits are correlated with a reduction of both ionotropic GABA A and metabotropic GABA B receptor–mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABA A receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABA A , Gabra1 ; GABA B , Gabbr1b ) in pyramidal neurons, and an enzyme that mediates GABA synthesis ( GAD65 ) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABA B receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABA B receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.

23 May 2024·Briefings in Bioinformatics

Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics

Article

Author: Huang, Wentao ; Lyu, Yanlin ; Sha, Weihong ; Qiu, Xinqi ; Chen, Hao ; Zeng, Ruijie ; Lian, Qizhou ; Jiang, Rui ; Chen, Jianyi ; Leung, Felix W ; Tong, Shuangshuang ; Luo, Ruibang ; Sun, Panpan ; Liu, Yufeng

AbstractAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which current treatments are limited and drug development costs are prohibitive. Identifying drug targets for ASD is crucial for the development of targeted therapies. Summary-level data of expression quantitative trait loci obtained from GTEx, protein quantitative trait loci data from the ROSMAP project, and two ASD genome-wide association studies datasets were utilized for discovery and replication. We conducted a combined analysis using Mendelian randomization (MR), transcriptome-wide association studies, Bayesian colocalization, and summary-data-based MR to identify potential therapeutic targets associated with ASD and examine whether there are shared causal variants among them. Furthermore, pathway and drug enrichment analyses were performed to further explore the underlying mechanisms and summarize the current status of pharmacological targets for developing drugs to treat ASD. The protein–protein interaction (PPI) network and mouse knockout models were performed to estimate the effect of therapeutic targets. A total of 17 genes revealed causal associations with ASD and were identified as potential targets for ASD patients. Cathepsin B (CTSB) [odd ratio (OR) = 2.66 95, confidence interval (CI): 1.28–5.52, P = 8.84 × 10−3], gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (OR = 1.99, 95CI: 1.06–3.75, P = 3.24 × 10−2), and formin like 1 (FMNL1) (OR = 0.15, 95CI: 0.04–0.58, P = 5.59 × 10−3) were replicated in the proteome-wide MR analyses. In Drugbank, two potential therapeutic drugs, Acamprosate (GABBR1 inhibitor) and Bryostatin 1 (CASP8 inhibitor), were inferred as potential influencers of autism. Knockout mouse models suggested the involvement of the CASP8, GABBR1, and PLEKHM1 genes in neurological processes. Our findings suggest 17 candidate therapeutic targets for ASD and provide novel drug targets for therapy development and critical drug repurposing opportunities.

01 Mar 2024·European Journal of Neuroscience

GABA_B receptor‐mediated modulation in the developing dorsal nucleus of the lateral lemniscus

Article

Author: Felmy, Felix ; Javadova, Amina

AbstractThe dorsal nucleus of the lateral lemniscus (DNLL) is a GABAergic, reciprocally connected auditory brainstem structure that continues to develop postnatally in rodents. One key feature of the DNLL is the generation of a strong, prolonged, ionotropic, GABAA receptor‐mediated inhibition. Possible GABAB receptor‐mediated signalling is unexplored in the DNLL. Here, we used Mongolian gerbils of either sex to describe GABAB receptor‐mediated modulation of postsynaptic potassium currents and synaptic inputs in postnatal (P) animals of days 10/11 and 23–28. Throughout development, we observed the presence of a Baclofen‐activated GABAB receptor‐enhanced potassium outward conductance that is capable of suppressing action potential generation. In P10/11, old gerbils GABAB receptor activation enhances glutamatergic and suppresses ionotropic GABAergic synaptic transmission. During development, this differential modulation becomes less distinct, because in P22–28, old animals Baclofen‐activated GABAB receptors rather enhance ionotropic GABAergic synaptic transmission, whereas glutamatergic transmission is both enhanced and suppressed. Blocking GABAB receptors causes an increase in ionotropic GABAergic transmission in P10/11 old gerbils that was independent on stimulation frequency but depended on the type of short‐term plasticity. Together with the lack of Baclofen‐induced changes in the synaptic paired‐pulse ratio of either input type, we suggest that GABAB receptor‐mediated modulation is predominantly postsynaptic and activates different signalling cascades. Thus, we argue that in DNLL neurons, the GABAB receptor is a post‐synaptically located signalling hub that alters signalling cascades during development for distinct targets.

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