Topic
GABAergic
About: GABAergic is a research topic. Over the lifetime, 9595 publications have been published within this topic receiving 473568 citations.
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TL;DR: It is concluded that gabapentin and pregabalin are not GABAergic and instead reduce the stimulated release of transmitters by binding at calcium channel alpha-delta (CaVa2-d) proteins.
Abstract: Gabapentin (Neurontin ) and pregabalin (Lyrica ) comprise an interesting class of drugs for chronic pain. These drugs differ structurally and mechanistically from other analgesics and also have efficacy in randomized trials for epileptic seizures and anxiety disorders. This paper highlights cellular and molecular mechanisms of these drugs that reduce pain. It is concluded that these drugs are not GABAergic and instead reduce the stimulated release of transmitters by binding at calcium channel alpha2-delta (CaVa2-d) proteins. The CaV nomenclature is useful to avoid confusion with unrelated adrenergic alpha receptors. Recent evidence suggests that CaVa2-d drugs also could reduce activity within certain cellular signaling pathways. The chemists who designed gabapentin and pregabalin endeavored to mimic the inhibitory neurotransmitter c-aminobutyric acid (GABA) in brain. However, later studies showed that this does not occur at relevant concentrations (see Section 3, below). Although sometimes called GABA derivatives or analogues (referring to chemical structure), this does not imply GABA-related pharmacology. Both compounds also differ from GABA because they readily cross membrane barriers via system L-amino acid transporters [36].
231 citations
TL;DR: A descending disynaptic inhibitory circuit that facilitates mechanical pain, is engaged during stress, and could be targeted to establish higher pain thresholds is uncovered.
230 citations
TL;DR: GA-mediated transmission is characterized by high variability of synaptic responses, and factors that determine synaptic GABA transients in the cleft, including diffusion and the actions of GABA transporters are investigated.
230 citations
TL;DR: Experimental data that point at the paradoxical role played by GABA(A) receptor-mediated mechanisms in synchronizing neuronal networks, and in particular those of limbic structures such as the hippocampus, the entorhinal and perirhinal cortices, are reviewed.
230 citations
TL;DR: The elements of this system provide for exquisite control of neuroendocrine activation in the face of stressful stimuli, and loss of this regulatory capacity may underlie many stress-related disorders.
Abstract: Neuronatomical and pharmacological studies have established GABA-mediated inhibition of the HPA axis at the level of the PVN. The origin of this innervation is a series of local hypothalamic and adjacent forebrain regions that project to stress-integrative hypophysiotropic CRH neurons. While a role in tonic inhibition of the stress axis is likely, this system of inhibitory loci is also capable of producing a dynamic braking capacity in the context of the neuroendocrine stress response. The latter function is mediated in large part by glutamatergic forebrain afferents that increase GABA release at the level of the PVN. In addition, this local GABA system can be inhibited by upstream GABAergic projection neurons, producing activation of the HPA axis via removal of GABAergic tone. This PVN projecting GABA network interfaces with a wide range of homeostatic mechanisms, and is capable of biochemical plasticity in response to chronic stress. Collectively, the elements of this system provide for exquisite control of neuroendocrine activation in the face of stressful stimuli, and loss of this regulatory capacity may underlie many stress-related disorders.
230 citations