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https://www.readbyqxmd.com/read/29677462/ondansetron-blocks-wildtype-and-p-f503l-variant-small-conductance-calcium-activated-potassium-channels
#1
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29658099/identification-of-serotoninergic-system-components-in-stallion-sperm
#2
F Jiménez-Trejo, I Coronado-Mares, M Boeta, I González-Santoyo, R Vigueras-Villaseñor, C Arriaga-Canon, L Herrera-Montalvo, M Tapia-Rodríguez
Assisted reproductive techniques have been used on several domestic animals to preserve desirable traits in strains of high genetic and commercial value; however in equines its efficiency rate is relatively low. To increase the conception ratio in stallions, some research groups have used pharmacological treatments which promote sperm hyperactivation in order to increase male's fertility rates. In this way, our previous work suggests that serotonin (5-HT) could be a good pharmacological candidate that facilitates conception rate in domestic horses...
April 16, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29655943/effects-of-a-histamine-h-4-receptor-antagonist-on-cisplatin-induced-anorexia-in-mice
#3
Kouichi Yamamoto, Rikuya Okui, Atsushi Yamatodani
Cancer chemotherapy often induces gastrointestinal symptoms such as anorexia, nausea, and vomiting. Antiemetic agents are effective in inhibiting nausea and vomiting, but patients still experience anorexia. We previously reported that chemotherapeutic agent-induced anorexia is associated with an increase of inflammatory cytokines. Other studies also reported that antagonism of the histamine H4 receptor is anti-inflammatory. In this study, we investigated the involvement of the H4 receptor in the development of chemotherapy-induced anorexia in mice...
April 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29649465/therapeutic-time-window-and-regulation-of-autophagy-by-mild-hypothermia-after-intracerebral-hemorrhage-in-rats
#4
Feifei Song, Cen Guo, Yang Geng, Xuqing Wu, Wei Fan
Although recent studies have shown that mild hypothermia has neuroprotective effects on intracerebral hemorrhage (ICH), the therapeutic time window of the therapy and the role of autophagy as a potential neuroprotective mechanism remain unclear. This study was aimed to investigate the appropriate time window of mild hypothermia and the regulation of autophagy during the treatment in a rat model of autologous blood-injected ICH injury. The rats were divided into Sham, normothermic (NT) and hypothermic (HT) groups...
April 9, 2018: Brain Research
https://www.readbyqxmd.com/read/29587564/mirtazapine-attenuates-nicotine-seeking-behavior-in-rats
#5
Susana Barbosa-Méndez, Alberto Salazar-Juárez
BACKGROUND: Nicotine is the major psychoactive component of tobacco. A number of pharmacological therapies have been evaluated, with poor results. Given the lack of success of these therapies, several authors have proposed alternative therapeutic strategies. One of these is the use of antidepressant drugs that may have a specific effect on the neural pathways or receptors underlying nicotine addiction. Mirtazapine is an antagonist of α2 NE receptors (noradrenergic receptor), 5-HT2A/C and 5-HT3 receptors and has demonstrated efficacy in reducing behavioral effects induced by drugs of abuse in human and animal models...
March 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29582424/antinociceptive-and-anti-inflammatory-effects-of-1-2-bis-4-methoxyphenylselanyl-styrene-in-mice-involvement-of-the-serotonergic-system
#6
Roberta Gonçalves Anversa, Fernanda Severo Sabedra Sousa, Paloma Taborda Birmann, David Borba Lima, Eder João Lenardão, César Augusto Bruning, Lucielli Savegnago
BACKGROUND: Pain is one of the most prevalent, costly and disabling conditions that reduces quality of life. Although there are many analgesics available, there is some concern regarding their efficacy, safety and side effects. Organic selenium compounds are attractive targets of various research groups due to their pharmacological properties. OBJECTIVES: The aim of this study was to evaluate the antinociceptive and anti-inflammatory activity of 1,2-bis-(4-methoxyphenylselanyl) styrene (BMOSE) in mice, as well as to investigate the mechanism involved in the antinociceptive effect...
March 27, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29566578/aminobenzisoxazole-compounds-as-agonists-of-%C3%AE-7-nicotinic-acetylcholine-receptors-a-patent-evaluation-wo-2017027600
#7
Yang He, Jingshan Shen
alpha 7 subtype nicotinic acetylcholine receptor (α7 nAChR) ligands, that is, ligands that interact with the orthosteric or allosteric binding sites of α7 nAChR, hold great potential for several therapeutic applications. Numerous compounds have been designed targeting α7 nAChR but most of them cannot be used therapeutically for various reasons. Areas covered: The patent application describes a series of germinal substituted aminobenzisoxazole compounds as α7 nAChR ligands. These compounds were claimed as potential therapeutics for treating and/or improving cognitive function...
March 23, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29559911/vortioxetine-treatment-reverses-subchronic-pcp-treatment-induced-cognitive-impairments-a-potential-role-for-serotonin-receptor-mediated-regulation-of-gaba-neurotransmission
#8
Alan L Pehrson, Christian S Pedersen, Kirstine Sloth Tølbøl, Connie Sanchez
Major depressive disorder (MDD) is associated with cognitive impairments that may contribute to poor functional outcomes. Clinical data suggests that the multimodal antidepressant vortioxetine attenuates some cognitive impairments in MDD patients, but the mechanistic basis for these improvements is unclear. One theory suggests that vortioxetine improves cognition by suppressing γ-amino butyric acid (GABA)ergic neurotransmission, thereby increasing glutamatergic activation. Vortioxetine's effects on cognition, GABA and glutamate neurotransmission have been supported in separate experiments, but no empirical work has directly connected vortioxetine's cognitive effects to those on GABA and glutamate neurotransmission...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29556812/getting-it-right-the-first-time-recent-progress-in-optimizing-antiemetic-usage
#9
Lee Schwartzberg
Recent years have witnessed significant improvements in the prevention and management of chemotherapy-induced nausea and vomiting (CINV), allowing patients to complete their prescribed chemotherapy regimens without compromising quality of life. This reduction in the incidence of CINV can be primarily attributed to the emergence of effective, well-tolerated antiemetic therapies, including serotonin (5-hydroxytryptamine or 5-HT3) receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and the atypical antipsychotic olanzapine...
March 19, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29548482/efficacy-of-neurokinin-1-receptor-antagonists-in-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-in-patients-receiving-carboplatin-based-chemotherapy-a-systematic-review-and-meta-analysis
#10
REVIEW
Massimo Di Maio, Chiara Baratelli, Paolo Bironzo, Francesca Vignani, Emilio Bria, Elisa Sperti, Maddalena Marcato, Fausto Roila
According to current ESMO - MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication...
April 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29547608/cisplatin-based-therapy-and-cinv-optimal-antiemetics-during-germ-cell-testicular-cancer-treatment
#11
Meghan Mastrangelo
BACKGROUND: Cisplatin-based chemotherapy regimens are the backbone of chemotherapy for germ cell testicular cancer. Cisplatin is administered for five days, causing an overlap of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Although CINV is widely researched, studies involving multiday chemotherapy regimens are limited. OBJECTIVES: This article synthesizes the research in antiemetics used in multiday cisplatin-based chemotherapy regimens and provides recommendations to optimize antiemetic therapy...
April 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29535986/efficacy-and-safety-of-ramosetron-injection-for-nausea-and-vomiting-in-colorectal-cancer-patients-undergoing-a-laparoscopic-colectomy-a-randomized-double-blind-comparative-study
#12
Han Eol Park, Min Ki Kim, Won-Kyung Kang
Purpose: A laparoscopic colectomy in colorectal-cancer patients is usually associated with a high risk of postoperative nausea and vomiting (PONV). The purpose of this study is to evaluate the efficacy of injection of long-acting 5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonist for the reduction of PONV in patients with colorectal cancer. Methods: A total of 48 patients scheduled to undergo a laparoscopic colectomy for colorectal cancer were randomized in a double-blinded fashion...
February 2018: Annals of Coloproctology
https://www.readbyqxmd.com/read/29535001/3-4-chlorophenylselanyl-1-methyl-1h-indole-a-new-selenium-compound-elicits-an-antinociceptive-and-anti-inflammatory-effect-in-mice
#13
Paloma T Birmann, Fernanda S S Sousa, Daniela H de Oliveira, Micaela Domingues, Beatriz M Vieira, Eder J Lenardão, Lucielli Savegnago
Several pathologies, such as pain and inflammation, are modulated by different pathways, making it necessary to develop drugs capable of modulating different pathways. Based on that, we investigated the antinociceptive and anti-inflammatory effect of 3-(4-chlorophenylselanyl)-1-methyl-1H-indole (CMI), as well as the systems involved in these actions. This study evaluated the antinociceptive and anti-inflammatory effects of CMI [0.0001-10mg/kg administered intragastrically (i.g.)] in the formalin, glutamate, hot plate, ear edema induced by croton oil and paw edema induced by formalin tests...
March 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29530351/gold-staging-system-is-appropriate-to-predict-mortality-in-older-people-with-chronic-obstructive-pulmonary-disease
#14
Claudio Pedone, Renato Giua, Nicola Scichilone, Vincenzo Bellia, Raffaele Antonelli-Incalzi
INTRODUCTION: In the new GOLD classification the reduction of FEV1, expressed as percentage of predicted value (FEV1PP), is considered an important prognostic factor. However, the use of FEV1PP may introduce bias, especially if based on equations derived from populations different from the one under study. We evaluated how well the GOLD classification stratifies the mortality risk when FEV1PP is based on an equation developed in the same population that gave rise to cases, externally developed equations, or as FEV1 divided by cubed height (FEV1/Ht3 )...
March 9, 2018: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29508995/characterization-of-a-5-ht-3-elic-chimera-revealing-the-sites-of-action-of-modulators
#15
Kerry L Price, Sarah C R Lummis
Cys-loop receptors are major sites of action for many important therapeutically active compounds, but the sites of action of those that do not act at the orthosteric binding site or at the pore are mostly poorly understood. To help understand these, we here describe a chimeric receptor consisting of the extracellular domain of the 5-HT3 A receptor and the transmembrane domain of a prokaryotic homologue, ELIC. Alterations of some residues at the coupling interface are required for function, but the resulting receptor expresses well and responds to 5-HT with a lower EC50 (0...
March 6, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29477299/serotonin-5ht-3-receptor-antagonism-potentiates-the-antidepressant-activity-of-citalopram
#16
Blanca Perez-Palomar, Irene Mollinedo-Gajate, Esther Berrocoso, J Javier Meana, Jorge E Ortega
Activation of serotonin 5-HT3 receptor (5HT3R) in the locus coeruleus (LC), the principal somatodendritic noradrenergic area, decreases LC firing activity and noradrenaline (NA) release in prefrontal cortex (PFC). Blockade of 5HT3R in coadministration with selective serotonin reuptake inhibitors (SSRIs) has been proposed as a potential strategy to accelerate the onset of action of SSRIs. Dual-probe microdialysis in rats was used to evaluate the involvement of 5HT3R in the in vivo effect exerted by the SSRI citalopram on NA release...
February 22, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29461426/emergent-management-of-primary-headache-a-review-of-current-literature
#17
Farnia Naeem, Chris Schramm, Benjamin W Friedman
PURPOSE OF REVIEW: The current article reviews recent data on treatment of acute headache patients in the acute care setting. RECENT FINDINGS: Intravenous fluid hydration, a common component of emergency department (ED) migraine therapy, does not improve pain outcomes and leads to longer ED lengths of stay. Therefore, intravenous fluids should be administered only to migraine patients with clinical evidence of dehydration. Similarly, intravenous ketamine has garnered interest as a treatment for acute pain but does not provide substantial relief to migraine patients...
February 15, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29430989/nk1r-5-ht1ar-interaction-is-related-to-the-regulation-of-melanogenesis
#18
Huali Wu, Yucheng Zhao, Qiaoling Huang, Minxuan Cai, Qi Pan, Mengsi Fu, Xiaohong An, Zhenjiang Xia, Meng Liu, Yu Jin, Ling He, Jing Shang
Substance P (SP) is a candidate mediator along the brain-skin axis and can mimic the effects of stress to regulate melanogenesis. Previously, we and others have found that the regulation of SP for pigmentary function was mediated by neurokinin 1 receptor (NK1R). Emerging evidence has accumulated that psychologic stress can induce dysfunction in the cutaneous serotonin 5-hydroxytryptamine (5-HT)-5-HT1A/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5-HTR (except 5-HT3) belong to GPCR...
February 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29413286/radiation-dose-to-the-thoracic-vertebral-bodies-is-associated-with-acute-hematologic-toxicities-in-patients-receiving-concurrent-chemoradiation-for-lung-cancer-results-of-a-single-center-retrospective-analysis
#19
Christian L Barney, Nicholas Scoville, Eric Allan, Ahmet Ayan, Dominic DiCostanzo, Karl E Haglund, John Grecula, Terence Williams, Meng Xu-Welliver, Gregory A Otterson, Jose G Bazan
PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V5 -V60 ) were retrospectively recorded...
March 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29412172/in-vitro-pharmacology-of-ambroxol-potential-serotonergic-sites-of-action
#20
J D Hull, R A Lyon
AIMS: Ambroxol is a muco-active agent with multiple, clinically relevant effects in the airway. Despite its widespread use and well documented clinical efficacy, there are few data on its mechanism of action and receptor pharmacology beyond sodium channel blockade and inhibition of guanylate cyclase. Accordingly, in vitro studies were conducted to determine its overall receptor pharmacology and possible sites of action. MATERIALS AND METHODS: In vitro radioligand binding/enzyme inhibition studies were conducted at 62 receptors, ion channels and enzymes using standard techniques...
February 2, 2018: Life Sciences
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