When benzodiazepines bind to a specific site on a GABA
gamma-Aminobutyric acid, or γ-aminobutyric acid, or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly respon…
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The benzodiazepines interact with benzodiazepine receptors that modulate GABA, an inhibitory neurotransmitter.
Benzodiazepine receptors, which are found on postsynaptic nerve endings in the central nervous system (CNS), are part of the GABA receptor complex. GABA is the primary inhibitory neurotransmitter of the CNS.
The Benzodiazepine Binding Sites of GABA A Receptors Everyday activity is based on a subtle equilibrium of excitatory and inhibitory neuronal systems. The most prominent players in neuronal inhibition are synaptic and extrasynaptic GABA<sub>A</sub> receptors.
Benzodiazepines have sedative, hypnotic, muscle-relaxant, and anticonvulsive effects, and are of outstandingly low overdose risk. The discovery of a large number of subtypes of GABAAreceptors has raised hopes for a clear separation of this spectrum of actions.
Benzodiazepine interactions with GABA receptors. Benzodiazepines (BZs) produce most, if not all, of their pharmacological actions by specifically enhancing the effects of endogenous and exogenous GABA that are mediated by GABAA receptors.
The unique feature of this drug receptor, which is located on a neurotransmitter receptor-gated ion channel, is its specific interaction with three classes of ligands. Agonists, competitive antagonists and inverse agonists at BZR, respectively increase, do not alter and reduce the gain of the GABA-R function.
The benzodiazepines interact with benzodiazepine receptors that modulate GABA, an inhibitory neurotransmitter. Benzodiazepine receptors are widely distributed in the CNS but are also present in kidney, liver, heart, and lung.38 The function of peripheral benzodiazepine receptors is unknown. 33 Of the GABA receptor subunits, GABA a appears to contain the benzodiazepine receptor, which is distinct from the GABA binding site. When benzodiazepines bind, gating for chloride channels is triggered, resulting in hyperpolarization of the cell and a decrease in neuronal excitation. 38 The effect on GABA appears to be the main mechanism by which benzodiazepines act, but a number of other neurotransmitters, including acetylcholine, catecholamines, serotonin, and glycine may be involved in benzodiazepine activity as well. 38
The benzodiazepine receptors are usually studied in the human brain using [11 C]flumazenil ( 11 C-FMZ), an antagonist with a high affinity and selectivity for central benzodiazepine receptors.
GABA activates the chloride ion channel, allowing chloride ions to enter the neuron. The flow of chloride ions into the neuron hyperpolarizes and inhibits the neuron. Benzodiazepines are metabolized in the liver by microsomal oxidation and glucuronidation.
PBRs in blood cells appear to play roles in several aspects of the immune response, such as phagocytosis and the secretion of interleukin-2, interleukin-3, and immunoglobulin A (IgA) (see review by Veenman and Gavish, 2006). In addition, the central benzodiazepine receptor may contribute to the regulation of T-cell function by modulating the activity of the hypothalamo-pituitary-adrenocortical axis, the sympathoadrenal system, or both, which, in turn, exert a significant effect on immune function (Zavala, 1997 ). Benzodiazepines bind to primary human microglial cells, the principal site of HIV-1 replication in the brain, and inhibit LPS-induced TNFalpha production by these cells in a concentration-dependent manner. Treatment of HIV-1-infected primary human microglial, as well as mixed glial/neuronal, cell cultures with benzodiazepines inhibits the expression of HIV-1 p24 antigen ( Lokensgard et al., 1998 ). Benzodiazepine-induced inhibition of HIV-1 expression in chronically infected promonocytic (U1) cells has been found to be associated with decreased activation of the nuclear transcription factor kappa B ( Lokensgard et al., 1998 ). Midazolam impairs neutrophil function at clinically relevant concentrations ( Nishina et al., 1998 ). Both the humoral and cell-mediated immune response of adult rats can be altered by administering diazepam prenatally or in early postnatal life ( Dostal et al., 1995; Schlumpf et al., 1992 ).
Benzodiazepines bind to primary human microglial cells, the principal site of HIV-1 replication in the brain, and inhibit LPS-induced TNFalpha production by these cells in a concentration-dependent manner.
GABA is the primary inhibitory neurotransmitter of the CNS. The GABA receptor complex is composed of two α-subunits and two β-subunits. The α-subunits are the binding sites for benzodiazepines. The β-subunits are the binding sites for GABA. A chloride ion channel is located in the center of the GABA receptor complex.
The benzodiazepine receptor and the gamma-amino-butyric acid (GABA) receptor form different parts of the same ionophore complex and both benzodiazepine and GABA-agonists inhibit brain activity. Several anticonvulsant drugs act through this mechanism.
Everyday activity is based on a subtle equilibrium of excitatory and inhibitory neuronal systems. The most prominent players in neuronal inhibition are synaptic and extrasynaptic GABA<sub>A</sub> receptors. Benzodiazepines are popular drugs that act as ...
The Benzodiazepine Binding Sites of GABA A Receptors. Everyday activity is based on a subtle equilibrium of excitatory and inhibitory neuronal systems. The most prominent players in neuronal inhibition are synaptic and extrasynaptic GABA<sub>A</sub> receptors. Benzodiazepines are popular drugs that act as positive allosteric modulators ...
The most prominent players in neuronal inhibition are synaptic and extrasynaptic GABAAreceptors. Benzodiazepines are popular drugs that act as positive allosteric modulators of a subset of these receptors. Benzodiazepines have sedative, hypnotic, muscle-relaxant, and anticonvulsive effects, and are of outstandingly low overdose risk.
Benzodiazepines have seda tive, hypnotic, muscle-relaxant, and anticonvulsive effects, and are of outstandingly low overdose risk. The discovery of a large number of subtypes of GABAAreceptors has raised hopes for a clear separation of this spectrum of actions.