HTR6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | HTR6, 5-HT6, 5-HT6R, 5-HT6 receptor, 5-hydroxytryptamine receptor 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 601109 MGI: 1196627 HomoloGene: 673 GeneCards: HTR6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). [5] It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. [5] HTR6 denotes the human gene encoding for the receptor. [6]
The 5HT6 receptor is expressed almost exclusively in the brain. [7] It is distributed in various areas including, but not limited to, the olfactory tubercle, cerebral cortex ( frontal and entorhinal regions), nucleus accumbens, striatum, caudate nucleus, hippocampus, and the molecular layer of the cerebellum. [5] [8] [9] Based on its abundance in extrapyramidal, limbic, and cortical regions it can be suggested that the 5HT6 receptor plays a role in functions like motor control, emotionality, cognition, and memory. [7] [9] [10]
Blockade of central 5HT6 receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas, [11] [12] [13] [14] whereas activation enhances GABAergic signaling in a widespread manner. [15] Antagonism of 5HT6 receptors also facilitates dopamine and norepinephrine release in the frontal cortex, [14] [16] while stimulation has the opposite effect. [15]
Despite the 5HT6 receptor having a functionally excitatory action, it is largely co-localized with GABAergic neurons and therefore produces an overall inhibition of brain activity. [15] In parallel with this, 5HT6 antagonists are hypothesized to improve cognition, learning, and memory. [17] Agents such as latrepirdine, idalopirdine (Lu AE58054), and intepirdine (SB-742,457/RVT-101) were evaluated as novel treatments for Alzheimer's disease and other forms of dementia. [14] [18] [19] However, phase III trials of latrepirdine, idalopirdine, and intepirdine have failed to demonstrate efficacy.
5HT6 antagonists have also been shown to reduce appetite and produce weight loss, and as a result, PRX-07034, BVT-5,182, and BVT-74,316 are being investigated for the treatment of obesity. [20] [21]
Recently, the 5HT6 agonists WAY-181,187 and WAY-208,466 have been demonstrated to be active in rodent models of depression, anxiety, and obsessive-compulsive disorder (OCD), and such agents may be useful treatments for these conditions. [15] [22] Additionally, indirect 5HT6 activation may play a role in the therapeutic benefits of serotonergic antidepressants like the selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).[ citation needed]
A large number of selective 5HT6 ligands have now been developed. [23] [24] [25] [26] [27] [28] [29] [30] [31]
Polymorphisms in the HTR6 gene are associated with neuropsychiatric disorders. For example, an association between the C267T ( rs1805054) polymorphism and Alzheimer's disease has been shown. [45] Others have studied the polymorphism in relation to Parkinson's disease. [46]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
HTR6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | HTR6, 5-HT6, 5-HT6R, 5-HT6 receptor, 5-hydroxytryptamine receptor 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 601109 MGI: 1196627 HomoloGene: 673 GeneCards: HTR6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). [5] It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. [5] HTR6 denotes the human gene encoding for the receptor. [6]
The 5HT6 receptor is expressed almost exclusively in the brain. [7] It is distributed in various areas including, but not limited to, the olfactory tubercle, cerebral cortex ( frontal and entorhinal regions), nucleus accumbens, striatum, caudate nucleus, hippocampus, and the molecular layer of the cerebellum. [5] [8] [9] Based on its abundance in extrapyramidal, limbic, and cortical regions it can be suggested that the 5HT6 receptor plays a role in functions like motor control, emotionality, cognition, and memory. [7] [9] [10]
Blockade of central 5HT6 receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas, [11] [12] [13] [14] whereas activation enhances GABAergic signaling in a widespread manner. [15] Antagonism of 5HT6 receptors also facilitates dopamine and norepinephrine release in the frontal cortex, [14] [16] while stimulation has the opposite effect. [15]
Despite the 5HT6 receptor having a functionally excitatory action, it is largely co-localized with GABAergic neurons and therefore produces an overall inhibition of brain activity. [15] In parallel with this, 5HT6 antagonists are hypothesized to improve cognition, learning, and memory. [17] Agents such as latrepirdine, idalopirdine (Lu AE58054), and intepirdine (SB-742,457/RVT-101) were evaluated as novel treatments for Alzheimer's disease and other forms of dementia. [14] [18] [19] However, phase III trials of latrepirdine, idalopirdine, and intepirdine have failed to demonstrate efficacy.
5HT6 antagonists have also been shown to reduce appetite and produce weight loss, and as a result, PRX-07034, BVT-5,182, and BVT-74,316 are being investigated for the treatment of obesity. [20] [21]
Recently, the 5HT6 agonists WAY-181,187 and WAY-208,466 have been demonstrated to be active in rodent models of depression, anxiety, and obsessive-compulsive disorder (OCD), and such agents may be useful treatments for these conditions. [15] [22] Additionally, indirect 5HT6 activation may play a role in the therapeutic benefits of serotonergic antidepressants like the selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).[ citation needed]
A large number of selective 5HT6 ligands have now been developed. [23] [24] [25] [26] [27] [28] [29] [30] [31]
Polymorphisms in the HTR6 gene are associated with neuropsychiatric disorders. For example, an association between the C267T ( rs1805054) polymorphism and Alzheimer's disease has been shown. [45] Others have studied the polymorphism in relation to Parkinson's disease. [46]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.