- |||||||||| Penthrox (methoxyflurane) / Medical Developments International, ByFavo (remimazolam) / PAION, Cosmo Pharma, Mundipharma, Pharmascience, Eagle Pharma
Review, Journal: The Role of GABA Receptors in Anesthesia and Sedation: An Updated Review. (Pubmed Central) - Oct 28, 2024
Ketamine, nitrous oxide, and xenon are not GABAR agonists and instead inhibit glutamate receptors-mainly NMDA receptors...Isoflurane and sevoflurane might have slightly different binding sites providing unexpected degree of selectivity...Penthrox (Galen, UK) is the special device designed for its administration...Remimazolam, a modified midazolam and methoxycarbonyl-etomidate (MOC-etomidate), an ultrashort-acting etomidate analog are two such examples...Carboetomidate is another soft analog of etomidate with low affinity for 11?-hydroxylase and is, therefore, unlikely to have clinically significant adrenocortical suppressant effects. Alphaxalone, a GABAAR agonist, is recently formulated in combination with 7-sulfobutylether-?-cyclodextrin (SBECD), which has a low hypersensitivity profile.
- |||||||||| Journal: Role of the K (Pubmed Central) - Oct 2, 2024
These findings suggest that the KF-PBN is a critical hub for the distribution of post-I activities to vagal and sympathetic outputs and is an important contributor to the dynamic adjustments to respiratory patterns that occur in response to acute hypoxia. While KF-PBN appears essential for post-I vagal activity, it only partially contributes to post-I sympathetic nerve activity, suggesting the contribution of multiple neural pathways to respiratory-sympathetic coupling.
- |||||||||| lorazepam / Generic mfg., memantine / Generic mfg.
Large-scale Dynamical Fingerprints of Distributed Synaptic Alterations in Early-Stage Psychosis (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12834;
Individual similarity to GABA-A effects was related to positive symptoms (e.g. delusions).We conclude that early-stage psychosis is associated with large-scale patterns of changes in cortical dynamics which result from alterations in GABA-A or NMDA receptor functions and differentially related to symptoms severity. Our approach opens new perspectives for a neurophysiological-biomarker assay of psychotic disorders.
- |||||||||| The inactivation of GABAA receptor dampens the promyelinating effects of lactation. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12357;
Furthermore, the GABAA receptor appears to promote the silencing of microglial activity in response to a demyelinating injury. This study paves the way for exploring the GABAA-mediated effects of breastfeeding in alleviating symptoms of demyelinating diseases such as multiple sclerosis.
- |||||||||| baclofen / Generic mfg.
Modulation of signal-to-noise ratio in CA1 pyramidal neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_10398;
To validate the sensitivity and reliability of this method in reflecting signal-to-noise ratio, we will apply a series of pharmacological agents known to modulate synaptic transmission (picrotoxin for GABAA receptor antagonism, CNQX for AMPA receptor antagonism, baclofen for GABAB receptor antagonism, and S-AMPA for AMPA receptor agonism)...Preliminary data indicate that this methodology proved sensitive to pharmacologically induced changes in signal and noise, validating SNR as a reliable measure of individual neuronal responses. This approach may have significant implications for understating the primary drivers of neuronal signal power and the excitatory/inhibitory balance in subpopulations of neurons.
- |||||||||| Theta burst stimulation of the perforant path increases bursting incidence in dentate gyrus granule cells (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_9851;
Computational modeling is essential for integrating mechanistic discoveries into a comprehensive understanding of neuronal information processing. This finding will allow us to test and improve biologically realistic computational DG models that aim to predict how neural circuits process sensory input, and how information is stored and retrieved during behavior.
- |||||||||| lorazepam / Generic mfg., memantine / Generic mfg.
Imaging the changes in cortex-wide human circuit dynamics under pharmacological manipulation of GABA-A and NMDA receptors (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_9185;
For the slope of the aperiodic component, these spatial patterns reflected not the anatomical hierarchy, but the cortical distribution of GABA-A receptor densities, with opposite directions for lorazepam and memantine effects.We conclude that controlled manipulations of specific synaptic receptors alter cortical dynamics along reliable and distinctive large-scale spatial patterns, which are partially explained by synaptic properties. These spatial patterns provide a reference for interpreting the patterns of corresponding changes due to the same manipulation during cognitive tasks or due to cognitive disorders in our ongoing work.
- |||||||||| Periaqueductal gray contributes to social approach and avoidance behaviors in rat (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8048;
The PAG is innervated by the insular cortex, which is also critical to social affective behaviors. Ongoing studies using intersectional viral genetic manipulations will characterize the subregions and cells of the PAG that are postsynaptic to insular afferents and determine whether an insular-PAG circuit is necessary for social affective behaviors.
- |||||||||| Dorsomedial prefrontal cortex controls the timing of locomotion and anticipatory licking during goal-directed behavior in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7543;
Here, we show that 1) the temporal control of locomotion and licking in this behavioral task is shaped and coordinated by both implicit and explicit reward information and 2) pharmacological inactivation of dmPFC disrupted the coordination of these motor behaviors leading to an increased number of failed trials. Our results suggest that dmPFC plays an important role in controlling the motor behavior based on reward expectations.
- |||||||||| The dorsal hippocampus is necessary to integrate and retrieve memories in sensory preconditioning (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7509;
Together, our results confirm that the hippocampus plays a critical role in sensory preconditioning and identify this role with regulation of activity in regions that encode the S2-S1 (PRh) and S1-US (BLA) memories. Thus, they shed light on how sensory and emotional memories are integrated such that events never paired with danger become frightening.
- |||||||||| eszopiclone / Generic mfg.
The Effect of Zolpidem on Sleep Physiology and Declarative Memory over a Nap in Schizophrenia (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6477;
We showed that although eszopiclone enhanced sleep spindles, it did not improve memory, potentially due to the disruption of spindle-SO coupling...Zolpidem may have increased isolated spindles, as coupled density was not affected despite an overall increase in spindle density. These findings are in line with prior research showing that coupled spindles are stronger predictors of memory than overall spindle activity.
- |||||||||| Tectin (tetrodotoxin) / CK Life Sci
Suprachiasmatic Nucleus Neuromedin S Neurons Provide GABAergic Monosynaptic input to Preoptic Area Kisspeptin Neurons in Mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6403;
Addition of 4-Aminopyridine (4-AP, a potassium channel blocker) to TTX rescued these responses, indicating the existence of a monosynaptic SCNNMS-to-POAKISS1 connection...Together, our findings provide direct evidence that monosynaptic GABAergic connections exist between SCNNMS neurons and POAKISS1 neurons. Further studies are needed to determine the impact of these projections on POAKISS1 neuron activity and the role they might play in the preovulatory surge.
- |||||||||| Mechanisms of ethanol-induced motor attacks in a mouse model of episodic ataxia type 2 (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5603;
However, neither ethanol nor furosemide affected the intrinsic firing of Purkinje cells in acute cerebellar slices of tottering mice, even though the firing of Purkinje cells during ethanol-induced attacks transforms to high frequency burst firing similar to that observed during stress and caffeine-induced attacks. Further experiments will shed more light on exactly how ethanol triggers attacks in the tottering mice with the goal of elucidating mechanisms underlying ethanol effects in EA2, and potentially more broadly in the CNS.
- |||||||||| Expression of angiotensin converting enzyme-2 (ACE2) modified by ischemic stroke and neurorehabilitation (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2270;
This study showed region-specific modifications of ACE2 expression in the brain after ischemic stroke, as if the increased ACE2 potentiated neuronal protection after stroke. it was suggested that the decrease of ACE2 expression caused by exercise could be attributed to a kind of compensation for the neuronal protection by exercise effect.
- |||||||||| Effect of BDNF on subicular circuits in vitro (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_998;
My interpretation is that BDNF treatment is sufficient to alter KCC2 function and leads to excitatory fast GABAergic transmission from (at least some) PVs that can recruit polysynaptic glutamatergic pathways generating the late depolarizing phase of the IPSP. These results have potential relevance for network signaling changes in the epileptic brain.
- |||||||||| Differential contribution of BDNF-TrkB signaling to hippocampal synaptic plasticity (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_967;
Similarly, chemically-induced LTP also required endogenous BDNF and TrkB signaling because it was inhibited by ANA-12 or K-252a. In contrast, HFS (100 Hz/1 sec) induced LTP that was not affected by TrkB receptor antagonism, indicating a differential role for endogenous BDNF depending on the induction paradigm.
- |||||||||| nimodipine / Generic mfg.
The GABAAreceptors modulate VEGF release and synthesis in M (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_325;
In contrast, HFS (100 Hz/1 sec) induced LTP that was not affected by TrkB receptor antagonism, indicating a differential role for endogenous BDNF depending on the induction paradigm. Moreover, extracellular calcium depletion by Ringer-Krebs medium Ca2+-free, BAPTA-AM, and the LTCC blocker nimodipine inhibits VEGF responses to GABA...Taken together, these data suggest that GABAA receptors have a role in the regulation of VEGF release and synthesis mechanism in mouse retinal M
- |||||||||| ByFavo (remimazolam) / PAION, Cosmo Pharma, Mundipharma, Pharmascience, Eagle Pharma
Journal: Macrophage WNK1 senses intracellular hypo-chlorine to regulate vulnerability to sepsis attack during hypochloremia. (Pubmed Central) - Aug 13, 2024
Remimazolam, as classic GABAa receptor agonist, alleviates excessive inflammation cascade by promoting macrophage chloride influx during sepsis progression. Collectively, this study proves that macrophage WNK1 acts as a negative regulator of inflammatory response by sensing chloride to maintain intracellular chloride balance during sepsis coupled with hypochloremia.
- |||||||||| Journal: Firing Patterns of Mitral Cells and Their Transformation in the Main Olfactory Bulb. (Pubmed Central) - Jul 27, 2024
Metabotropic glutamate receptors also played a role in LLCs in MCs. These pieces of evidence indicate that odor information can be encoded on a mitral cell (MC) platform, where it can be relayed to higher-order olfactory centers through intrinsic and dendrodendritic mechanisms in MCs.
- |||||||||| ByFavo (remimazolam) / PAION, Cosmo Pharma, Mundipharma, Pharmascience, Eagle Pharma
Utility of Remimazolam Versus Propofol for Total Intravenous Anesthesia: A Meta-analysis (Exhibit Hall) - Jun 25, 2024 - Abstract #ASA2024ASA_2057;
The pooled analysis showed no difference in the time to initial loss of consciousness with remimazolam versus propofol (mean difference [MD] = 20.18 seconds, 95% confidence interval [CI] = -7.56, 47.93). There was a statistically significant difference between extubation times for patients receiving remimazolam versus propofol, such that the remimazolam group was extubated faster than the propofol group [MD = -2.38 minutes, CI = -3.97, -0.80] (Figure 1).
- |||||||||| Review, Journal: Dimdazenil: First Approval. (Pubmed Central) - Jun 20, 2024
On 29 November 2023, dimdazenil oral capsules received approval in China for the short-term treatment of insomnia. This article summarizes the milestones in the development of dimdazenil leading to this first approval for insomnia.
- |||||||||| Anorexia Induced by the Central Action of Fibroblast Growth Factor 1 (FGF1) Is Dependent on Activation of Parabrachial CGRP Neurons (Poster Hall (West A4-B2); 1523) - May 20, 2024 - Abstract #ADA2024ADA_3009;
Finally, we bilaterally infected CGRPPBN neurons with either AAV1-DIO-hM4Di:mCherry or AAV1-DIO-mCherry control virus and observed that inhibition of CGRPPBN neurons following administration of CNO fully reversed FGF1-induced anorexia in hM4Di-bearing mice, while anorexia remained intact in the mCherry control group. Together, these data suggest that FGF1-induced anorexia results from reduced GABAergic inhibition of CGRPPBN neurons.
- |||||||||| Anorexia Induced by the Central Action of Fibroblast Growth Factor 1 (FGF1) Is Dependent on Activation of Parabrachial CGRP Neurons (Exhibit Hall (West A1-A3) ePoster Theater B; 1523) - May 20, 2024 - Abstract #ADA2024ADA_2364;
Finally, we bilaterally infected CGRPPBN neurons with either AAV1-DIO-hM4Di:mCherry or AAV1-DIO-mCherry control virus and observed that inhibition of CGRPPBN neurons following administration of CNO fully reversed FGF1-induced anorexia in hM4Di-bearing mice, while anorexia remained intact in the mCherry control group. Together, these data suggest that FGF1-induced anorexia results from reduced GABAergic inhibition of CGRPPBN neurons.
- |||||||||| ByFavo (remimazolam) / PAION, Cosmo Pharma, Mundipharma, Pharmascience, Eagle Pharma
Journal: Remimazolam Improves the Markers of Post-Resuscitation Cerebral Injury in a Swine Model of Cardiac Arrest. (Pubmed Central) - Apr 30, 2024
Together, these data suggest that FGF1-induced anorexia results from reduced GABAergic inhibition of CGRPPBN neurons. In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of post-resuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.
- |||||||||| dizocilpine (MK801) / Merck (MSD)
Review, Journal: Vestibular compensation: Neural mechanisms and clinical implications for the treatment of vertigo. (Pubmed Central) - Apr 1, 2024
The declining frequency of spontaneous nystagmus after UL is an index of the initial process, and short-term administration of diazepam, a GABAA receptor agonist, has been shown to accelerate the initial process in rats...The declining number of MK801-induced Fos-positive neurons in contra-MVe after UL is an index of the late process, and long-term administration of betahistine, a histamine H3 receptor antagonist, has been shown to accelerate the late process in rats...To facilitate dynamic vestibular compensation, early ambulation and subsequent vestibular rehabilitation exercise are recommended for the treatment of chronic vertigo in patients with uncompensated unilateral vestibular dysfunction. Although vestibular compensation after bilateral vestibular loss is not expected, vestibular rehabilitation with a sensory-substitution strategy can improve imbalance in patients with bilateral vestibular lesions.
- |||||||||| gaboxadol (OV101) / Ovid Therapeutics, Angelini Group, Healx
Preclinical, Journal: Enhancing GABAergic tonic inhibition reduces seizure-like activity in the neonatal mouse hippocampus and neocortex. (Pubmed Central) - Feb 16, 2024
There has been no significant improvement in treating neonatal seizures for nearly 50 years, especially for patients in whom pharmacoresistance develops. Our results show that enhancing tonic inhibition in neonatal mice, a developmental age when GABA mainly depolarizes, decreases neuronal firing and epileptiform activity in vitro Our results suggest that augmenting tonic inhibition could be an alternative treatment for neonatal seizures, especially in pharmacy-resistant ones.
- |||||||||| Journal: Application of ensemble learning for predicting GABA receptor agonists. (Pubmed Central) - Feb 8, 2024
Our results show that enhancing tonic inhibition in neonatal mice, a developmental age when GABA mainly depolarizes, decreases neuronal firing and epileptiform activity in vitro Our results suggest that augmenting tonic inhibition could be an alternative treatment for neonatal seizures, especially in pharmacy-resistant ones. Overall, our ensemble learning-based model (PubMac-GB) achieved comparable performance and would be helpful in effectively identifying agonists of GABAA receptors.
- |||||||||| ivabradine / Generic mfg.
Preclinical, Journal: The role of HCN channels on the effects of T-type calcium channels and GABA receptors in the absence epilepsy model of WAG/Rij rats. (Pubmed Central) - Feb 8, 2024
In this study we used ivabradine (IVA), a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, to identify its effect on spike-wave discharges (SWDs); and aimed to determine the role of IVA on the effects of T-type calcium channel blocker NNC 55-0396, GABAA receptor agonist muscimol and antagonist bicuculline in male WAG/Rij rats...Subacute administration of IVA reduced the antiepileptic activity of NNC, while the proepileptic activity of muscimol and the antiepileptic activity of bicuculline were abolished. It might be suggested that subacute IVA administration reduces absence seizures by changing the HCN channel expressions in WAG/Rij rats, and this affects the T-type calcium channels and GABA receptors.
- |||||||||| Autoregulation of striatal dopamine release by co-released GABA dampens phasic-to-tonic dopamine signaling (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_11273;
Importantly, however, the differential effect of PTX on optically-evoked phasic-to-tonic DA signaling was lost in mice devoid of GAT1 in DA neurons and lack GABA co-release. Together, these data provide evidence for direct autoinhibition of axonal DA release by co-released GABA that is likely faster than G-protein coupled D2 autoreceptors, thereby introducing a novel autoregulatory mechanism by which co-released GABA acts as a first responder to dampen phasic-to-tonic DA signaling.
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