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https://www.readbyqxmd.com/read/28730747/study-of-the-prevalence-of-5-ht-2c-receptor-gene-polymorphisms-in-egyptian-patients-with-lifelong-premature-ejaculation
#1
M F Roaiah, Y I Elkhayat, L A Rashed, S F GamalEl Din, A M El Guindi, M A Abd El Salam
We investigated the prevalence of 5HT2C receptor gene polymorphisms in Egyptian patients with lifelong premature ejaculation. A total of 350 participants were enrolled in a prospective study. Two hundred and forty-five cases with lifelong premature ejaculation joined this study, in addition to 105 controls. We instructed the partners of the cases to measure the IELT of the first intercourse only using a stopwatch for 1 month. Genotyping was carried out at the end of the study. The results showed that the majority of the patients and controls were Cys/Cys...
July 21, 2017: Andrologia
https://www.readbyqxmd.com/read/28664341/the-activity-of-the-serotonin-receptor-2c-is-regulated-by-alternative-splicing
#2
REVIEW
Stefan Stamm, Samuel B Gruber, Alexander G Rabchevsky, Ronald B Emeson
The central nervous system-specific serotonin receptor 2C (5HT2C) controls key physiological functions, such as food intake, anxiety, and motoneuron activity. Its deregulation is involved in depression, suicidal behavior, and spasticity, making it the target for antipsychotic drugs, appetite controlling substances, and possibly anti-spasm agents. Through alternative pre-mRNA splicing and RNA editing, the 5HT2C gene generates at least 33 mRNA isoforms encoding 25 proteins. The 5HT2C is a G-protein coupled receptor that signals through phospholipase C, influencing the expression of immediate/early genes like c-fos...
June 29, 2017: Human Genetics
https://www.readbyqxmd.com/read/28578215/effects-of-agomelatine-on-pentylenetetrazole-induced-kindling-kindling-associated-oxidative-stress-and-behavioral-despair-in-mice-and-modulation-of-its-actions-by-luzindole-and-1-m-chlorophenyl-piperazine
#3
M Suhaib Azim, Nidhi B Agarwal, Divya Vohora
In view of well-evidenced antiepileptic effects of melatonin and few reports of anticonvulsant action of agomelatine, the present study investigated whether agomelatine protects against pentylenetetrazole (PTZ)-induced kindling in mice and kindling-associated oxidative stress, depression, and impairment of spatial memory. In order to explore whether effects are mediated by melatonergic or serotonergic mechanisms, 1-(m-chlorophenyl) piperazine (mCPP), selective 5HT2c receptor agonist and luzindole, melatonergic receptor antagonist, were taken as pharmacological tools...
June 1, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28438504/agomelatine-protects-against-neuronal-damage-without-preventing-epileptogenesis-in-the-kainate-model-of-temporal-lobe-epilepsy
#4
Jana Tchekalarova, Dimitrinka Atanasova, Zlatina Nenchovska, Milena Atanasova, Lidia Kortenska, Rumyana Gesheva, Nikolai Lazarov
Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE)...
April 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28385157/comparative-analysis-of-a-to-i-editing-in-human-and-non-human-primate-brains-reveals-conserved-patterns-and-context-dependent-regulation-of-rna-editing
#5
Richard T O'Neil, Xiaojing Wang, Michael V Morabito, Ronald B Emeson
A-to-I RNA editing is an important process for generating molecular diversity in the brain through modification of transcripts encoding several proteins important for neuronal signaling. We investigated the relationships between the extent of editing at multiple substrate transcripts (5HT2C, MGLUR4, CADPS, GLUR2, GLUR4, and GABRA3) in brain tissue obtained from adult humans and rhesus macaques. Several patterns emerged from these studies revealing conservation of editing across primate species. Additionally, variability in the human population allows us to make novel inferences about the co-regulation of editing at different editing sites and even across different brain regions...
April 6, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28289278/cafeteria-diet-and-probiotic-therapy-cross-talk-among-memory-neuroplasticity-serotonin-receptors-and-gut-microbiota-in-the-rat
#6
J E Beilharz, N O Kaakoush, J Maniam, M J Morris
The western diet is known to have detrimental effects on cognition and the gut microbiota, but few studies have investigated how these may be related. Here, we examined whether a probiotic could prevent diet-induced memory deficits. Rats were pre-exposed to vehicle, low or high doses of VSL#3 for 2 weeks before half were switched from chow to a cafeteria diet (Caf) for 25 days; VSL#3 treatment continued until death. High-dose VSL#3 prevented the diet-induced memory deficits on the hippocampal-dependent place task, but the probiotic caused deficits on the perirhinal-dependent object task, irrespective of diet or dose...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogs-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#7
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena López-Ferreras, Elin Banke, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt Asterholm, Christophe M Lamy, Karolina P Skibicka
Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation...
April 2017: Diabetes
https://www.readbyqxmd.com/read/27933810/structure-based-scaffold-repurposing-for-g-protein-coupled-receptors-transformation-of-adenosine-derivatives-into-5ht2b-5ht2c-serotonin-receptor-antagonists
#8
Dilip K Tosh, Antonella Ciancetta, Eugene Warnick, Steven Crane, Zhan-Guo Gao, Kenneth A Jacobson
Adenosine derivatives developed to activate adenosine receptors (ARs) revealed micromolar activity at serotonin 5HT2B and 5HT2C receptors (5HTRs). We explored the structure-activity relationship at 5HT2Rs and modeled receptor interactions in order to optimize affinity and simultaneously reduce AR affinity. Depending on N(6) substitution, small 5'-alkylamide modification maintained 5HT2BR affinity, which was enhanced upon ribose substitution with rigid bicyclo[3.1.0]hexane (North (N)-methanocarba), e.g., N(6)-dicyclopropylmethyl 4'-CH2OH derivative 14 (Ki 11 nM)...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27931246/increased-alternate-splicing-of-htr2c-in-a-mouse-model-for-prader-willi-syndrome-leads-disruption-of-5ht2c-receptor-mediated-appetite
#9
Alastair S Garfield, Jennifer R Davies, Luke K Burke, Hannah V Furby, Lawrence S Wilkinson, Lora K Heisler, Anthony R Isles
Alternate splicing of serotonin (5-hydroxytryptamine; 5-HT) 2C receptor (5-HT2CR) pre-RNA is negatively regulated by the small nucleolar RNA, Snord115, loss of which is observed in nearly all individuals with Prader-Willi Syndrome (PWS), a multigenic disorder characterised by hyperphagia and obesity. Given the role of the 5-HT2CR in the regulation of ingestive behaviour we investigated the pathophysiological implications of Snord115 deficiency on 5-HT2CR regulated appetite in a genotypically relevant PWS mouse model (PWS-IC)...
December 8, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27738375/ziprasidone-augmentation-in-an-adolescent-with-obsessive-compulsive-disorder-a-case-report
#10
Sevcan Karakoç Demirkaya, Behiye Alyanak
Obsessive compulsive disorder (OCD) is characterized by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions). Although selective serotonin reuptake inhibitors are widely used to treat OCD, only half of the patients respond well. Several potentiation strategies including off-label use of antipsychotics (mostly risperidone, quetiapine) have been tried. Ziprasidone is an atypical antipsychotic with the best affinity ratio of 5 HT 2A/D2 and 5HT2C/D2 receptors. There is a limited data on ziprasidone in pediatric groups...
March 1, 2016: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/27600945/the-%C3%AE-1-opioid-receptor-and-5-ht2a-and-5ht2c-serotonergic-receptors-of-the-locus-coeruleus-are-critical-in-elaborating-hypoalgesia-induced-by-tonic-and-tonic-clonic-seizures
#11
Renato Leonardo de Freitas, Priscila Medeiros, Juliana Almeida da Silva, Rithiele Cristina de Oliveira, Ricardo de Oliveira, Farhad Ullah, Asmat Ullah Khan, Norberto Cysne Coimbra
It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia. The goal of this study was to examine if LC-opioid and serotonergic/noradrenergic mechanisms signal the post-ictal hypoalgesic responses to tonic-clonic seizures produced by intraperitoneal administration of pentylenetetrazole (PTZ at 64mg/kg), causing an ionophore γ-aminobutyric acid (GABA)-mediated Cl(-) influx antagonism...
November 12, 2016: Neuroscience
https://www.readbyqxmd.com/read/27593622/h1-histamine-receptor-affinity-predicts-weight-gain-with-antidepressants
#12
Virginio Salvi, Claudio Mencacci, Francesco Barone-Adesi
Weight gain and metabolic abnormalities are extensively found in patients taking psychotropic medications. Although mainly antipsychotics have been implicated, also antidepressants carry the potential to induce weight gain, with tricyclics and mirtazapine being associated with the greatest weight gain. It has been suggested that this could be due to the different ability of antidepressants to block adrenergic, cholinergic, and histaminergic postsynaptic receptors. To date, however, the link between antidepressant-induced weight gain and their receptor affinity profile has not been established...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27511837/control-of-sensory-neuron-excitability-by-serotonin-involves-5ht2c-receptors-and-ca-2-activated-chloride-channels
#13
Isabella Salzer, Enkhbileg Gantumur, Arsalan Yousuf, Stefan Boehm
Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27503570/mechanism-of-action-of-pimavanserin-in-parkinson-s-disease-psychosis-targeting-serotonin-5ht2a-and-5ht2c-receptors
#14
Stephen M Stahl
Pimavanserin, a novel agent approved for the treatment of Parkinson's disease psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A receptors and less potent antagonist/inverse agonist actions at 5HT2C receptors.
August 2016: CNS Spectrums
https://www.readbyqxmd.com/read/27222264/current-trends-on-antipsychotics-focus-on-asenapine
#15
REVIEW
Donatella Marazziti, Armando Piccinni, Stefano Baroni, Francesco Mungai, Silvio Presta, Federico Mucci, Liliana Dell'Osso
Over the years, both first- (FGAs) and second-generation antipsychotics (SGAs), continue to gain increasing evidence of being effective in the treatment of psychotic symptoms. Currently, they represent the first-line treatment of schizophrenia and bipolar disorder, although they are widely used in psychotic depression and other clinical conditions, such as agitation and/or behavioural disturbances. Despite representing an indispensable tool for the treatment of severe psychotic disorders, they are widely known to have a number of unwanted side effects that the clinician must be aware of, and handle carefully to provide the patient the best available treatment in the short and long-term...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/26655822/serotonin-increases-synaptic-activity-in-olfactory-bulb-glomeruli
#16
Julia Brill, Zuoyi Shao, Adam C Puche, Matt Wachowiak, Michael T Shipley
Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs)...
March 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/26444951/agomelatine-for-depression-in-parkinson-disease-additional-effect-on-sleep-and-motor-dysfunction
#17
Asuncion Avila, Xavier Cardona, Montserrat Martin-Baranera, Lucia Leon, Nuria Caballol, Pablo Millet, Juan Bello
Depression and sleep disorders are among the most prevalent nonmotor symptoms of Parkinson disease (PD). Because agomelatine acts as a MT1 and MT2 agonist and as a 5HT2c antagonist, this study was designed to assess the efficacy of agomelatine in treating depressive symptoms in PD patients, and the potential changes both in sleep quality and motor symptoms. Depressed patients with PD were treated with agomelatine for 6 months, and they were evaluated with an array of scales. Completed nocturnal video-polysomnography was performed at baseline and week 12...
December 2015: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/26346394/horizons-in-the-pharmacotherapy-of-obesity
#18
REVIEW
Jonathan R S Arch
Obesity drugs have had a chequered history. In the recent past, only the low efficacy, pancreatic lipase inhibitor orlistat was available worldwide and it was little used. The 5HT2C agonist, lorcaserin, and two combinations of old drugs have been approved in the United States but not in Europe. The diabetes drug liraglutide has been approved in both the US and Europe and seems likely to be most widely accepted. In view of regulators' caution in approving obesity drugs, some (like beloranib) may initially be progressed for niche obesity markets...
December 2015: Current Obesity Reports
https://www.readbyqxmd.com/read/26255180/preclinical-characterization-of-toluene-as-a-non-classical-hallucinogen-drug-in-rats-participation-of-5-ht-dopamine-and-glutamate-systems
#19
María Teresa Rivera-García, Carolina López-Rubalcava, Silvia L Cruz
RATIONALE: Toluene is a misused inhalant with hallucinogenic properties and complex effects. Toluene blocks N-methyl-D-aspartate (NMDA) receptors, releases dopamine (DA), and modifies several neurotransmitter levels; nonetheless, the mechanism by which it produces hallucinations is not well characterized. OBJECTIVES: This study aims (a) to study toluene's effects on the 5-HT2A-mediated head-twitch response (HTR), dopamine (DA), and serotonin (5-HT) tissue levels in discrete brain regions; (b) to compare the actions of toluene, ketamine, and 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) on HTR; and (c) to study the pharmacological blockade of toluene's and ketamine's effects by selective drugs...
October 2015: Psychopharmacology
https://www.readbyqxmd.com/read/26174133/does-melatonin-treatment-change-emotional-processing-implications-for-understanding-the-antidepressant-mechanism-of-agomelatine
#20
Abbie Pringle, Maria Bogdanovskaya, Poppy Waskett, Sophie Zacharia, Philip J Cowen, Catherine J Harmer
The antidepressant, agomelatine, has a novel pharmacological profile, with agonist properties at M1 and M2 receptors and antagonist properties at 5HT2C receptors. Whether the antidepressant effects of this treatment are mediated by the drug's effects at the M1 and M2 receptors or the 5HT2C receptor or a synergy between these actions remains unclear. In the present study, a healthy volunteer model of emotional processing, which discriminates between effective and non-effective antidepressant compounds, was used to assess the contribution of melatonin agonism to the efficacy of agomelatine...
October 2015: Journal of Psychopharmacology
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