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https://www.readbyqxmd.com/read/28099839/trpc5-mediates-acute-leptin-and-serotonin-effects-via-pomc-neurons
#1
Yong Gao, Ting Yao, Zhuo Deng, Jong-Woo Sohn, Jia Sun, Yiru Huang, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hong Chen, Hongbo Guo, Jianqun Yan, Kathryn A Cunningham, Yongsheng Chang, Tiemin Liu, Kevin W Williams
The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28073790/clemizole-and-modulators-of-serotonin-signalling-suppress-seizures-in-dravet-syndrome
#2
Aliesha Griffin, Kyla R Hamling, Kelly Knupp, SoonGweon Hong, Luke P Lee, Scott C Baraban
Dravet syndrome is a catastrophic childhood epilepsy with early-onset seizures, delayed language and motor development, sleep disturbances, anxiety-like behaviour, severe cognitive deficit and an increased risk of fatality. It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal voltage-activated sodium channel. Zebrafish with a mutation in the SCN1A homologue recapitulate spontaneous seizure activity and mimic the convulsive behavioural movements observed in Dravet syndrome. Here, we show that phenotypic screening of drug libraries in zebrafish scn1 mutants rapidly and successfully identifies new therapeutics...
January 10, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28029083/psychopathological-behaviour-and-cognition-in-morbid-obesity
#3
Alba Calderone, Pasquale Fabio Calabrò, Chita Lippi, Roberta Jaccheri, Jacopo Vitti, Ferruccio Santini
BACKGROUND: Obesity is a chronic condition with high prevalence and multifaceted aetiology, accompanied by an increased risk of morbidity and mortality. Obesity has several negative effects on the psychological status, and the severity of psychological disorders correlates with the degree of obesity. OBJECTIVE: Aim of this review is to provide an overview of the literature concerning the psychological distress associated with severe obesity, which contributes to deterioration of the quality of life of affected patients...
December 26, 2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
https://www.readbyqxmd.com/read/27971740/cost-utility-analysis-of-lorcaserin-in-the-treatment-of-obesity
#4
Z Sharif, M Peikanpour, M Rangchian, M J Foroughi Moghadam
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
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
#5
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/27888609/effects-of-lorcaserin-on-pre-existing-valvulopathy-a-pooled-analysis-of-phase-3-trials
#6
Neil J Weissman, Steven R Smith, Randi Fain, Nancy Hall, William R Shanahan
OBJECTIVE: To evaluate the effects of lorcaserin in patients with pre-existing Food and Drug Administration (FDA)-defined valvulopathy. METHODS: This is a pooled, post hoc analysis of three Phase 3 studies. BLOOM and BLOSSOM patients were 18 to 65 years of age without diabetes and with a body mass index (BMI) of 27 to 29.9 kg/m(2) and ≥1 weight-related comorbidity or a BMI of 30 to 45 kg/m(2) . BLOOM-DM patients had a BMI of 27 to 45 kg/m(2) and type 2 diabetes...
January 2017: Obesity
https://www.readbyqxmd.com/read/27882999/activation-of-ventral-tegmental-area-5-ht2c-receptors-reduces-incentive-motivation
#7
Lourdes Valencia-Torres, Cristian M Olarte-Sánchez, David J Lyons, Teodora Georgescu, Megan Greenwald-Yarnell, Martin G Myers, Christopher M Bradshaw, Lora K Heisler
Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice...
December 21, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27857126/repeated-7-day-treatment-with-the-5-ht2c-agonist-lorcaserin-or-the-5-ht2a-antagonist-pimavanserin-alone-or-in-combination-fails-to-reduce-cocaine-vs-food-choice-in-male-rhesus-monkeys
#8
Matthew L Banks, S Stevens Negus
Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0...
December 14, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27852796/combination-varenicline-and-lorcaserin-for-tobacco-dependence-treatment-and-weight-gain-prevention-in-overweight-and-obese-smokers-a-pilot-study
#9
Ryan T Hurt, Ivana T Croghan, Darrell R Schroeder, J Taylor Hays, Doo-Sup Choi, Jon O Ebbert
INTRODUCTION: Post-cessation weight gain (PCWG) is a major barrier to maintaining abstinence, especially in weight-concerned smokers. Varenicline is the most effective medication for smoking cessation but has minimal impact on PCWG. Lorcaserin is an FDA-approved medication for weight management in overweight or obese patients which also provides a noticeable benefit in treating drug dependence. We hypothesized that combining varenicline with lorcaserin may help prevent PCWG. We conducted an open-label, single arm, Phase II clinical pilot study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing PCWG in overweight and obese smokers...
November 16, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/27815511/lorcaserin-for-smoking-cessation-and-associated-weight-gain-a-randomized-12-week-clinical-trial
#10
William R Shanahan, Jed E Rose, Alan Glicklich, Scott Stubbe, Matilde Sanchez-Kam
INTRODUCTION: Lorcaserin is a selective serotonin 2C receptor agonist approved by the FDA for chronic weight management. Preclinical data suggest that it may also be effective in smoking cessation through modulation of the dopaminergic reward system. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled trial conducted in 30 centers in the United States. 603 adult smokers with a Body Mass Index (BMI) of 18.5-35 kg/m(2), averaging at least 10 cigarettes/day with no period of abstinence >3 months for the past year were randomized to lorcaserin 10 mg QD, 10 mg BID or placebo; all received standardized smoking cessation counseling weekly...
November 4, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/27773782/obesity-current-and-potential-pharmacotherapeutics-and-targets
#11
REVIEW
Vidya Narayanaswami, Linda P Dwoskin
Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior...
October 20, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27718159/reward-induced-eating-therapeutic-approaches-to-addressing-food-cravings
#12
REVIEW
Candida J Rebello, Frank L Greenway
The homeostatic controls over eating are inextricably linked to the reward aspects of eating. The result is an integrated response that coordinates the internal milieu with the prevailing environment. Thus, appetite, which reflects a complex interaction among the external environment, behavioral profile, and subjective states as well as the storage and metabolism of energy, has an important role in the regulation of energy balance. In the prevailing food environment which offers an abundance of food choices it is likely that the motivation to consume from a wide range of delectable foods plays a greater role in contributing to overeating than in the past when the motivation to eat was largely governed by metabolic need...
November 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27708788/a-randomized-open-label-pilot-of-the-combination-of-low-level-laser-therapy-and-lorcaserin-for-weight-loss
#13
Ivana T Croghan, Jon O Ebbert, Darrell R Schroeder, Ryan T Hurt, Victoria Hagstrom, Matthew M Clark
BACKGROUND: Obesity is a significant public health problem and innovative treatments are needed. The purpose of this pilot study was to assess the preliminary efficacy and safety of a combined treatment of low-level laser therapy (LLLT) and lorcaserin on weight loss, health quality of life (QOL) measures, and cardiovascular risk factors. METHODS: Forty-five overweight and obese adult participants with a body mass index (BMI) >26.9 and <40 were randomized to receive LLLT, lorcaserin, or a combination of the two therapies...
2016: BMC Obesity
https://www.readbyqxmd.com/read/27692638/single-and-multiple-dose-pharmacokinetics-of-a-lorcaserin-extended-release-tablet
#14
Ronald Christopher, Mike Morgan, Jim Ferry, Bhaskar Rege, Yong Tang, Allan Kristensen, William Shanahan
PURPOSE: Lorcaserin is a serotonin 2C receptor agonist indicated for chronic weight management as an adjunct to diet and exercise. The initial approved formulation is a 10-mg, immediate-release (IR) tablet for administration BID. These studies investigated the single- and multiple-dose pharmacokinetic properties of a new, recently US Food and Drug Administration-approved, extended-release, 20-mg once-daily formulation. METHODS: We performed 2 separate 2-period, 2-sequence crossover studies in 36 healthy adults: a study comparing the IR formulation to the extended-release formulation under fasting conditions and a study comparing the extended-release formulation under fed and fasted conditions...
October 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27659698/lorcaserin-treatment-allows-for-decreased-number-needed-to-treat-for-weight-and-glycemic-parameters-in-week-12-responders-with-%C3%A2-5-weight-loss
#15
Yehuda Handelsman, Randi Fain, Zhixiao Wang, Xuan Li, Ken Fujioka, William Shanahan
OBJECTIVES: Lorcaserin is a serotonin 2C receptor agonist approved for chronic weight management. This analysis explores the number of patients needed to be treated (NNT) with lorcaserin for one more patient to achieve weight loss and glycemic goals. METHODS: This is a post hoc analysis of three Phase 3 studies in adults with and without type 2 diabetes mellitus (T2DM) treated with lorcaserin 10 mg BID or placebo. NNT is reported for patients achieving ≥5% or ≥10% weight loss, achievement of either HbA1c <5...
November 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27650954/effects-of-lorcaserin-on-cocaine-and-methamphetamine-self-administration-and-reinstatement-of-responding-previously-maintained-by-cocaine-in-rhesus-monkeys
#16
Lisa R Gerak, Gregory T Collins, Charles P France
Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin2C [5-hydroxytryptamine2C (5-HT2C)] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion)...
December 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27640338/characterization-of-the-discriminative-stimulus-effects-of-lorcaserin-in-rats
#17
Katherine M Serafine, Kenner C Rice, Charles P France
Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0...
September 2016: Journal of the Experimental Analysis of Behavior
https://www.readbyqxmd.com/read/27627785/safety-and-tolerability-review-of-lorcaserin-in-clinical-trials
#18
REVIEW
F L Greenway, W Shanahan, R Fain, T Ma, D Rubino
Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials...
October 2016: Clinical Obesity
https://www.readbyqxmd.com/read/27583422/update-on-office-based-strategies-for-the-management-of-obesity
#19
Michael Erlandson, Laurie C Ivey, Katie Seikel
Obesity is a common condition that is associated with numerous medical problems such as cardiovascular disease, pulmonary disease, and diabetes mellitus. Primary care physicians have an important role in helping patients develop a successful weight loss plan to improve their overall health. Dietary strategies emphasizing reduced caloric intake, regardless of the nutrient composition, are important for weight loss. Behavioral interventions such as motivational interviewing and encouraging physical activity lead to additional weight loss when combined with dietary changes...
September 1, 2016: American Family Physician
https://www.readbyqxmd.com/read/27565106/answers-to-clinical-questions-in-the-primary-care-management-of-people-with-obesity-pharmacologic-management
#20
Ken Fujioka, Jill Braverman-Panza
The recent approval of liraglutide, lorcaserin, naltrexone/bupropion extended-release, and phentermine/topiramate extended-release, brings the number of medications for long-term weight loss to 5 (including orlistat). Indicated for the treatment of patients with overweight (body mass index [BMI] ≥27 kg/m2 with ≥1 weight-related comorbidity) or obesity (BMI ≥30 kg/m2), these medications provide new opportunities to address this burgeoning health problem.
July 2016: Journal of Family Practice
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