GHB: Difference between revisions

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==Pharmacology==

GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | http://www.sciencedirect.com/science/article/pii/S0149763489800533</ref> in the central nervous system. GHB is an agonist at the newly characterized GHB receptor, which is excitatory,<ref>γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> and it is a weak agonist at the [[GABA]]B receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref>

GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | http://www.sciencedirect.com/science/article/pii/S0149763489800533</ref> in the central nervous system. GHB is an [[agonist]] at the newly characterized GHB receptor, which is excitatory,<ref>γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> and it is a weak [[agonist]] at the [[GABA]]B receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref>

GHB induces the accumulation of either a derivative of tryptophan or tryptophan itself ~~in the extracellular space~~, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

GHB induces the accumulation of either a derivative of [[tryptophan]] or [[tryptophan]] itself, possibly by increasing [[tryptophan]] transport across the blood–brain barrier. GHB-induced stimulation may be due to an increase in [[tryptophan]] transport to the brain and in its uptake by [[Serotonin|serotonergic]] cells. As the [[Serotonin|serotonergic]] system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]B receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABAB antagonists.

However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]B receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABAB [[antagonists]].

The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]B agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>

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 ==Pharmacology==
-GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | http://www.sciencedirect.com/science/article/pii/S0149763489800533</ref> in the central nervous system. GHB is an agonist at the newly characterized GHB receptor, which is excitatory,<ref>γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> and it is a weak agonist at the [[GABA]]<sub>B</sub> receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref>
+GHB has at least two distinct binding sites<ref>Gammahydroxybutyrate: An endogenous regulator of energy metabolism | http://www.sciencedirect.com/science/article/pii/S0149763489800533</ref> in the central nervous system. GHB is an [[agonist]] at the newly characterized GHB receptor, which is excitatory,<ref>γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence | http://www.sciencedirect.com/science/article/pii/S0028390804002527</ref><ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref> and it is a weak [[agonist]] at the [[GABA]]<sub>B</sub> receptor, which is inhibitory.<ref>A mechanism for γ-hydroxybutyrate (GHB) as a drug and a substance of abuse | http://www.medecinesciences.org/articles/medsci/abs/2005/03/medsci2005213p284/medsci2005213p284.html</ref>
-GHB induces the accumulation of either a derivative of tryptophan or tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.
+GHB induces the accumulation of either a derivative of [[tryptophan]] or [[tryptophan]] itself, possibly by increasing [[tryptophan]] transport across the blood–brain barrier. GHB-induced stimulation may be due to an increase in [[tryptophan]] transport to the brain and in its uptake by [[Serotonin|serotonergic]] cells. As the [[Serotonin|serotonergic]] system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.
-However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]<sub>B</sub> receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABA<sub>B</sub> antagonists.
+However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates [[GABA]]<sub>B</sub> receptors, which are primarily responsible for its sedative effects.<ref>Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> GHB's sedative effects are blocked by GABA<sub>B</sub> [[antagonists]].
 The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref> Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and [[GABA]]<sub>B</sub> agonists.<ref>Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid | http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02037.x/abstract</ref>