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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
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...
October 7, 2016: Advances in Therapy
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
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...
September 27, 2016: Clinical Therapeutics
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...
September 23, 2016: Postgraduate Medicine
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-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)...
September 20, 2016: Journal of Pharmacology and Experimental Therapeutics
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
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
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
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
Pingwen Xu, Yanlin He, Xuehong Cao, Lourdes Valencia-Torres, Xiaofeng Yan, Kenji Saito, Chunmei Wang, Yongjie Yang, Antentor Hinton, Liangru Zhu, Gang Shu, Martin G Myers, Qi Wu, Qingchun Tong, Lora K Heisler, Yong Xu
BACKGROUND: Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. METHODS: We combined neuroanatomic, pharmacologic, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-hydroxytryptamine (5-HT) 2C receptor (5-HT2CR) expressed by dopamine (DA) neurons in the regulation of binge-like eating behavior in mice. RESULTS: We showed that 5-HT stimulates DA neural activity through a 5-HT2CR-mediated mechanism, and activation of this midbrain 5-HT→DA neural circuit effectively inhibits binge-like eating behavior in mice...
June 9, 2016: Biological Psychiatry
Xavier Pi-Sunyer, William Shanahan, Randi Fain, Tony Ma, W Timothy Garvey
OBJECTIVES: Treatment guidelines for type 2 diabetes mellitus (T2DM) suggest weight loss as a means to maintain glycemic control. Lorcaserin has been approved for chronic weight management in the United States as an adjunct to a reduced-calorie diet and exercise, and the previous phase 3 Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus (BLOOM-DM) study has shown that, in addition to weight loss, lorcaserin is associated with improvements in glycemic parameters...
August 2016: Postgraduate Medicine
Olivia M Farr, Jagriti Upadhyay, Anna Gavrieli, Michelle Camp, Nikolaos Spyrou, Harper Kaye, Hannah Mathew, Maria Vamvini, Anastasia Koniaris, Holly Kilim, Alexandra Srnka, Alexandra Migdal, Christos S Mantzoros
Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state...
October 2016: Diabetes
Ziad Omran
Obesity is growing at an alarming rate with huge consequences on health and economy. The worldwide prevalence of obesity has nearly doubled in 30 years. Obesity causes many physiological dysfunctions that affect nearly every organ producing multiple morbidities. Despite these facts, there is still no clear, well-defined solution. Notwithstanding the devastating prevalence and consequences of obesity, today only five medicines, orlistat, lorcaserin, phentermine-toprimate, bupropion-naltrexone and liraglutide, are approved by the FDA for long-term treatment of obesity...
June 16, 2016: Mini Reviews in Medicinal Chemistry
Rohan Khera, Mohammad Hassan Murad, Apoorva K Chandar, Parambir S Dulai, Zhen Wang, Larry J Prokop, Rohit Loomba, Michael Camilleri, Siddharth Singh
IMPORTANCE: Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE: To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION: Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo...
June 14, 2016: JAMA: the Journal of the American Medical Association
Guy A Higgins, Leo B Silenieks, Everett B Altherr, Cam MacMillan, Paul J Fletcher, Wayne E Pratt
RATIONALE: The 5-HT2C receptor agonist lorcaserin (Belviq®) has been approved by the FDA for the treatment of obesity. Impulsivity is a contributory feature of some eating disorders. OBJECTIVE: Experiments investigated the effect of lorcaserin and the highly selective 5-HT2C agonist CP-809101 on measures of impulsivity and on reinstatement of food-seeking behaviour, a model of dietary relapse. The effect of both drugs on 22-h deprivation-induced feeding was also examined, as was the effect of prefeeding in each impulsivity test...
July 2016: Psychopharmacology
Maite Solas, Fermin I Milagro, Diego Martínez-Urbistondo, Maria J Ramirez, J Alfredo Martínez
Five pharmaceutical strategies are currently approved by the US FDA for the treatment of obesity: orlistat, lorcaserin, liraglutide, phentermine/topiramate, and bupropion/naltrexone. The most effective treatment seems to be the combined administration of phentermine/topiramate followed by lorcaserin and bupropion/naltrexone. In relation to the management of excessive weight, other aspects also need to be considered, including comorbidities accompanying obesity, drug interactions, and the risk of negative collateral effects, as well as individualized treatments based on the genetic make-up...
July 2016: Trends in Pharmacological Sciences
Charles T Nguyen, Sharon Zhou, William Shanahan, Randi Fain
PURPOSE: Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown...
June 2016: Clinical Therapeutics
Katherine H Saunders, Rekha B Kumar, Leon I Igel, Louis J Aronne
Obesity is a growing epidemic in the USA with over one third of adults presently classified as obese. Obesity-related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and certain types of cancer. Modest weight loss of 5-10 % of body weight is sufficient to produce clinically relevant improvements in cardiovascular disease risk factors among patients with overweight and obesity. Until recently, there were limited pharmacologic options approved by the Food and Drug Administration to treat obesity...
July 2016: Current Atherosclerosis Reports
C Apovian, K Palmer, R Fain, C Perdomo, D Rubino
Body composition was determined using dual-energy X-ray absorptiometry (DXA) in a subset of patients without (BLOSSOM) and with (BLOOM-DM) type 2 diabetes who received diet and exercise counselling along with either lorcaserin 10 mg twice daily or placebo. DXA scans were performed on study day 1 (baseline), week 24 and week 52. Baseline demographics of the subpopulations (without diabetes, n = 189; with diabetes, n = 63) were similar between studies and representative of their study populations. At week 52, patients without diabetes on lorcaserin lost significantly more fat mass relative to those on placebo (-12...
September 2016: Diabetes, Obesity & Metabolism
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