Neurotransmitters and Receptors in the Basal Ganglia
W. R. Wayne Martin in Functional Imaging in Movement Disorders, 2019
GABA is the neurotransmitter used by the majority of neurons in the striatum, lateral and medial pallidum, and the substantia nigra pars reticulata.23,24 Two classes of GABA receptors have been defined, GABAA and GABAB receptors. The GABAA receptors are postsynaptic receptors mediating chloride flux. These receptors are bicuculline-sensitive and are the classic GABA receptors mediating GABAergic inhibition. GABAB receptors also appear to mediate inhibition but through bicuculline-insensitive receptors. The GABAB receptor is located both presynaptically on the terminals of neurons which use transmitters other than GABA and postsynaptically. There are no selective antagonists at the GABAB receptor and the only selective agonist is baclofen.
Neurotransmitters and pharmacology
Mark J. Ashley, David A. Hovda in Traumatic Brain Injury, 2017
Two subtypes of GABA receptor have been described in detail and are referred to as GABAA and GABAB receptors. The GABAA receptor has been more thoroughly investigated and is a ligand-gated ion channel that functions as a channel for the chloride ion.136,147,148 This receptor is usually placed in a gene superfamily that also includes the nicotinic acetylcholine receptor, 5-HT3 receptor, and the glycine receptor. This gene superfamily is sometimes called the cys-loop family, which distinguishes it from the excitatory amino acid ligand-gated channel family of receptors.136 GABAA receptors are stimulated by GABA, muscimol, and isoguvacine and are blocked by the convulsants bicuculline (competitive antagonist) and picrotoxin (noncompetitive antagonist). The GABAA receptor is a heteropentamer composed of five polypeptide subunits forming the chloride ion channel in the cell membrane. The GABAA receptor contains several distinct binding sites for different chemicals that can modulate its function (see the following).
Overview of Neurotransmission: Relationship to the Action of Antiepileptic Drugs
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
Two subtypes of GABA receptor have been described and are referred to as GABAA and GABAB subtypes. The GABAA receptor has been more thoroughly investigated. It is said to be one of a superfamily of ligand-gated ion channels that evolved from a common ancestral receptor.95,96 This family also includes the nicotinic acetylcholine receptor and the glycine receptor. GABAA receptors are stimulated by GABA, muscimol, and isoguvacine and are inhibited by the convulsants bicuculline (competitively) and picrotoxin (noncom-petitively). The GABAA receptor appears to exist in a macromolecular complex which consists of the GABA recognition site, the chloride channel, and the benzodiazepine-binding site.
Trending gabapentin exposures in Kentucky after legislation requiring use of the state prescription drug monitoring program for all opioid prescriptions#
Published in Clinical Toxicology, 2019
Kiran A. Faryar, Ashley N. Webb, Bikash Bhandari, Timothy G. Price, George M. Bosse
Gabapentin is a gamma-aminobutyric acid (GABA) analog structurally related to the GABA neurotransmitter although it does not interact with GABA receptors or inhibit GABA uptake or degradation [1]. Gabapentin also binds to the alpha-2-delta subunit of calcium channels, which inhibits calcium current and decreases neurotransmitter release. Binding at this receptor has been associated with anticonvulsant activity [2,3]. It is approved by the US Food and Drug Administration (FDA) for the treatment of partial seizures and post-herpetic neuralgia [4,5]. Clinically, it is frequently used off-label for a wide array of medical conditions including mood disorders, posttraumatic stress disorder, behavioral disorders [6], restless leg syndrome, cocaine withdrawal, insomnia, neuropathy[7], tremors, and chronic pain [8,9]. Gabapentin has a wide therapeutic window and few serious adverse side effects with therapeutic use [4]. Side effects are non-specific and include somnolence, dizziness, ataxia, fatigue, nystagmus, and movement disorder [6,10].
GABA and l -theanine mixture decreases sleep latency and improves NREM sleep
Published in Pharmaceutical Biology, 2019
Suhyeon Kim, Kyungae Jo, Ki-Bae Hong, Sung Hee Han, Hyung Joo Suh
GABA acts through GABA receptors. There are generally 2 types of GABA receptors: GABAA and GABAB. The most important receptor, with respect to sleep is the GABAA receptor (Gottesmann 2002). When GABA or another agonist binds to GABAA receptor, it triggers the influx of chloride ions in neuronal cells. This causes a negative membrane potential that inhibits action potential firing. In this way, GABA (and GABA-promoting compounds) reduce activity in brain cells through GABAA receptor activation. It is well-known that the activation of GABAA receptors is beneficial for sleep (Abdou et al. 2006). The structural similarity of l-theanine to the neurotransmitter glutamic acid has prompted researchers to study its potential competition binding on glutamate receptors in the nervous system (Shinozaki and Ishida 1978). l-Theanine rapidly induces changes in serotonergic and dopaminergic transmission (Yokogoshi et al. 1998). These components act as modulating receptors of the neurotransmitter GABA, which is the main inhibitory neurotransmitter in the CNS, and therefore, one of the main molecules responsible for sleeping behaviour (Zanoli and Zavatti 2008). The decreases in sleep latency, together with a slight improvement in sleep quality, are the possible reasons for the observed increase in sleep efficiency, in our study.
Emerging therapeutic targets for schizophrenia: a framework for novel treatment strategies for psychosis
Published in Expert Opinion on Therapeutic Targets, 2021
Susan F. Sonnenschein, A Grace
Compounds that target the GABA system aim to restore normal patterns of PV+ interneuron activity. Indeed, transplants of GABA interneuron precursor cells into the hippocampus of MAM rats have been shown to normalize hippocampal pyramidal neuron activity and DA neuron population activity, demonstrating that restoring GABA function is sufficient to normalize the aberrant hippocampus-DA circuit [73]. Increased GABA signaling can also be accomplished through direct modulation of GABA receptors. Broad action GABA modulators, such as benzodiazepines are problematic due to their sedative actions, risk of dependency and inferiority in reducing psychotic symptoms compared to current antipsychotics in patients with chronic schizophrenia [74], but other, more localized options, have been studied for their potential therapeutic value.
Related Knowledge Centers
- Central Nervous System
- Gabaa Receptor
- Inhibitory Postsynaptic Potential
- Neurotransmitter
- Receptor
- Γ-Aminobutyric Acid
- Gabab Receptor
- Ligand-Gated Ion Channel
- Ionotropic Effect
- G Protein-Coupled Receptor