The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Jaime M Monti - One of the best experts on this subject based on the ideXlab platform.
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the effects of benzodiazepine and nonbenzodiazepine agents ramelteon low dose doxepin suvorexant and selective serotonin 5 ht2a receptor antagonists and inverse agonists on sleep and wakefulness
Clinical Medicine Insights: Therapeutics, 2016Co-Authors: Jaime M Monti, Pablo Torterolo, Seithikurippu R PandiperumalAbstract:Several agents are known to improve sleep induction and/or maintenance in patients with insomnia disorder. These include the benzodiazepine (BZD) and non-BZD receptor allosteric modulators, the melatonin receptor agonist ramelteon, low-dose doxepin, and suvorexant. One of the drawbacks of the BZDs is their known reduction in both N3 sleep [also known as slow wave sleep or delta sleep and characterized by the occurrence of slow high amplitude delta (0.5–2 Hz) waves] and rapid eye movement (REM) sleep. Low-dose doxepin has shown similar association with decrease in REM sleep. By contrast, suvorexant increases REM sleep. The available evidence tends to indicate that irrespective of their mechanisms of action, the selective serotonin 5-HT2A receptor antagonists and inverse agonists, including Volinanserin, pruvanserin, and nelotanserin, when given in isolated administration, increases slow wave sleep in laboratory animals. Wakefulness and REM sleep were decreased in some studies. Moreover, subjects with normal sleep showed significant increase in N3 sleep following the administration of eplivanserin, nelotanerin, and pimavanserin. Nelotanserin has also been shown to augment N3 sleep in patients with chronic insomnia disorder. N2 sleep tended to decrease in most of these studies, while REM sleep showed no significant changes. Taken together, these evidences suggest that the coadministration of a selective 5-HT2A receptor antagonist or inverse agonist with a hypnotic drug could be a valid clinical strategy for normalizing sleep induction and maintenance and for promoting N3 sleep in patients with insomnia disorder. Additionally, the 5-HT2A receptor agents may have a potential value for improving the cognition and memory deficits in patients with a chronic insomnia disorder as well as elderly patients who show reductions in N3 sleep.
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The Effects of Benzodiazepine and Nonbenzodiazepine Agents, Ramelteon, Low-dose Doxepin, Suvorexant, and Selective Serotonin 5-HT Receptor Antagonists and Inverse Agonists on Sleep and Wakefulness
SAGE Publishing, 2016Co-Authors: Jaime M Monti, Pablo Torterolo, Seithikurippu R. Pandi-perumalAbstract:Several agents are known to improve sleep induction and/or maintenance in patients with insomnia disorder. These include the benzodiazepine (BZD) and non-BZD receptor allosteric modulators, the melatonin receptor agonist ramelteon, low-dose doxepin, and suvorexant. One of the drawbacks of the BZDs is their known reduction in both N3 sleep [also known as slow wave sleep or delta sleep and characterized by the occurrence of slow high amplitude delta (0.5–2 Hz) waves] and rapid eye movement (REM) sleep. Low-dose doxepin has shown similar association with decrease in REM sleep. By contrast, suvorexant increases REM sleep. The available evidence tends to indicate that irrespective of their mechanisms of action, the selective serotonin 5-HT 2A receptor antagonists and inverse agonists, including Volinanserin, pruvanserin, and nelotanserin, when given in isolated administration, increases slow wave sleep in laboratory animals. Wakefulness and REM sleep were decreased in some studies. Moreover, subjects with normal sleep showed significant increase in N3 sleep following the administration of eplivanserin, nelotanerin, and pimavanserin. Nelotanserin has also been shown to augment N3 sleep in patients with chronic insomnia disorder. N2 sleep tended to decrease in most of these studies, while REM sleep showed no significant changes. Taken together, these evidences suggest that the coadministration of a selective 5-HT 2A receptor antagonist or inverse agonist with a hypnotic drug could be a valid clinical strategy for normalizing sleep induction and maintenance and for promoting N3 sleep in patients with insomnia disorder. Additionally, the 5-HT 2A receptor agents may have a potential value for improving the cognition and memory deficits in patients with a chronic insomnia disorder as well as elderly patients who show reductions in N3 sleep
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serotonin control of sleep wake behavior
Sleep Medicine Reviews, 2011Co-Authors: Jaime M MontiAbstract:Summary Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) functions predominantly to promote wakefulness (W) and to inhibit REM (rapid eye movement) sleep (REMS). Yet, under certain circumstances the neurotransmitter contributes to the increase in sleep propensity. Most of the serotonergic innervation of the cerebral cortex, amygdala, basal forebrain (BFB), thalamus, preoptic and hypothalamic areas, raphe nuclei, locus coeruleus and pontine reticular formation comes from the dorsal raphe nucleus (DRN). The 5-HT receptors can be classified into at least seven classes, designated 5-HT 1–7 . The 5-HT 1A and 5-HT 1B receptor subtypes are linked to the inhibition of adenylate cyclase, and their activation evokes a membrane hyperpolarization. The actions of the 5-HT 2A , 5-HT 2B and 5-HT 2C receptor subtypes are mediated by the activation of phospholipase C, with a resulting depolarization of the host cell. The 5-HT 3 receptor directly activates a 5-HT-gated cation channel which leads to the depolarization of monoaminergic, aminoacidergic and cholinergic cells. The primary signal transduction pathway of 5-HT 6 and 5-HT 7 receptors is the stimulation of adenylate cyclase which results in the depolarization of the follower neurons. Mutant mice that do not express 5-HT 1A or 5-HT 1B receptor exhibit greater amounts of REMS than their wild-type counterparts, which could be related to the absence of a postsynaptic inhibitory effect on REM-on neurons of the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT). 5-HT 2A and 5-HT 2C receptor knock-out mice show a significant increase of W and a reduction of slow wave sleep (SWS) which has been ascribed to the increase of catecholaminergic neurotransmission involving mainly the noradrenergic and dopaminergic systems. Sleep variables have been characterized, in addition, in 5-HT 7 receptor knock-out mice; the mutants spend less time in REMS that their wild-type counterparts. Direct infusion of the 5-HT 1A receptor agonists 8-OH-DPAT and flesinoxan into the DRN significantly enhances REMS in the rat. In contrast, microinjection of the 5-HT 1B (CP-94253), 5-HT 2A/2C (DOI), 5-HT 3 (m-chlorophenylbiguanide) and 5-HT 7 (LP-44) receptor agonists into the DRN induces a significant reduction of REMS. Systemic injection of full agonists at postsynaptic 5-HT 1A (8-OH-DPAT, flesinoxan), 5-HT 1B (CGS 12066B, CP-94235), 5-HT 2C (RO 60-0175), 5-HT 2A/2C (DOI, DOM), 5-HT 3 (m-chlorophenylbiguanide) and 5-HT 7 (LP-211) receptors increases W and reduces SWS and REMS. Of note, systemic administration of the 5-HT 2A/2C receptor antagonists ritanserin, ketanserin, ICI-170,809 or sertindole at the beginning of the light period has been shown to induce a significant increase of SWS and a reduction of REMS in the rat. Wakefulness was also diminished in most of these studies. Similar effects have been described following the injection of the selective 5-HT 2A receptor antagonists Volinanserin and pruvanserin and of the 5-HT 2A receptor inverse agonist nelotanserin in rodents. In addition, the effects of these compounds have been studied on the sleep electroencephalogram of subjects with normal sleep. Their administration was followed by an increase of SWS and, in most instances, a reduction of REMS. The administration of ritanserin to poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder caused a significant increase in SWS. The 5-HT 2A receptor inverse agonist APD-125 induced also an increase of SWS in patients with chronic primary insomnia. It is known that during the administration of benzodiazepine (BZD) hypnotics to patients with insomnia there is a further reduction of SWS and REMS, whereas both variables tend to remain decreased during the use of non-BZD derivatives (zolpidem, zopiclone, eszopiclone, zaleplon). Thus, the association of 5-HT 2A antagonists or 5-HT 2A inverse agonists with BZD and non-BZD hypnotics could be a valid alternative to normalize SWS in patients with primary or comorbid insomnia.
Byron Creese - One of the best experts on this subject based on the ideXlab platform.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:Background Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. Methods Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and Volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. Results Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). Conclusions These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
bioRxiv, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:INTRODUCTION: Stroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHOD: Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and Volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository. RESULTS: Atherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection). CONCLUSION: These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
Yasaman Malekizadeh - One of the best experts on this subject based on the ideXlab platform.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:Background Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. Methods Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and Volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. Results Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). Conclusions These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
bioRxiv, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:INTRODUCTION: Stroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHOD: Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and Volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository. RESULTS: Atherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection). CONCLUSION: These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
Clive Ballard - One of the best experts on this subject based on the ideXlab platform.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:Background Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. Methods Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and Volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. Results Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). Conclusions These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
bioRxiv, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:INTRODUCTION: Stroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHOD: Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and Volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository. RESULTS: Atherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection). CONCLUSION: These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
Gareth Williams - One of the best experts on this subject based on the ideXlab platform.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:Background Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. Methods Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and Volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. Results Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). Conclusions These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
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whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
bioRxiv, 2020Co-Authors: Yasaman Malekizadeh, Gareth Williams, Mark Kelson, David Whitfield, Jonathan Mill, David A Collier, Clive Ballard, Aaron R Jeffries, Byron CreeseAbstract:INTRODUCTION: Stroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHOD: Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and Volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository. RESULTS: Atherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection). CONCLUSION: These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
