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Gitanjali Srivastava, Caroline Apovian
PURPOSE OF REVIEW: Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity...
March 5, 2018: Current Obesity Reports
Maksim L Maksimov, Andrey A Svistunov, Vadim V Tarasov, Vladimir N Chubarev, Marco Ávila-Rodriguez, George E Barreto, Olga V Dralova, Gjumrakch Aliev
Obesity and metabolic syndrome (MS) are risk factors for diabetes, cancer, some cardiovascular and musculoskeletal diseases. Pharmacotherapy should be used when the body mass index (BMI) exceeds 30 kg/m² or 27 kg/m² with comorbidity. Efficacy and safety of pharmacotherapy depend on the mechanism of action of drugs. In this context, drugs affecting the central and peripheral mediator systems such as cannabinoid receptor antagonists (Rimonabant), neuronal reuptake inhibitor of NE and 5 HT (Sibutramine), neuronal reuptake inhibitor of NE 5-HT DA (Tesofensine), agonist of 5 HT 2C receptors (Lorcaserin) have a high risk of side effects on the central nervous and cardiovascular systems when used for a long period...
2016: Current Pharmaceutical Design
David J Heal, Jane Gosden, Sharon L Smith
The long held view is cocaine's pharmacological effects are mediated by monoamine reuptake inhibition. However, drugs with rapid brain penetration like sibutramine, bupropion, mazindol and tesofensine, which are equal to or more potent than cocaine as dopamine reuptake inhibitors, produce no discernable subjective effects such as drug "highs" or euphoria in drug-experienced human volunteers. Moreover they are dysphoric and aversive when given at high doses. In vivo experiments in animals demonstrate that cocaine's monoaminergic pharmacology is profoundly different from that of other prescribed monoamine reuptake inhibitors, with the exception of methylphenidate...
December 2014: Neuropharmacology
Lieuwe Appel, Mats Bergström, Jørgen Buus Lassen, Bengt Långström
Tesofensine (TE) is a novel triple monoamine re-uptake inhibitor inducing a potent inhibition of the re-uptake process in the synaptic cleft of the neurotransmitters dopamine, norepinephrine, and serotonin. In recent preclinical and clinical evaluations TE showed a robust anti-obesity effect, but the specific mechanism of this triple monoamine re-uptake inhibitor still needs to be further elucidated. This positron emission tomography (PET) study, using [¹¹C]βCIT-FE, aimed to assess the degree of the dopamine transporter (DAT) occupancy, at constant TE plasma levels, following different oral, multiple doses of TE during totally 8-12 days...
February 2014: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Melvin George, Muthukumar Rajaram, Elangovan Shanmugam
Obesity has become a growing pandemic of alarming proportions in the developed and developing countries over the last few decades. The most perturbing fact regarding obesity is the increased predisposition for coronary artery disease, congestive heart failure and sudden cardiac death. The modest efficacy of current anti-obesity agents such as orlistat and the increasing withdrawals of several anti-obesity agents such as sibutramine, rimonabant have led to huge gaps in the pharmacotherapy of obesity. Lorcaserin and Phentermine-topiramate combination (phen-top) are two drugs approved by US FDA in 2012...
January 2014: Journal of Cardiovascular Pharmacology and Therapeutics
Henrik H Hansen, Majbrit M Jensen, Agnete Overgaard, Pia Weikop, Jens D Mikkelsen
Tesofensine is a triple monoamine reuptake inhibitor which inhibits noradrenaline, 5-HT and dopamine reuptake. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong and sustained effects in obesity management is not clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity...
September 2013: Pharmacology, Biochemistry, and Behavior
Bo Hjorth Bentzen, Morten Grunnet, Lars Hyveled-Nielsen, Claus Sundgreen, Jørgen Buus Lassen, Henrik H Hansen
OBJECTIVE: Tesofensine is a novel triple monoamine reuptake inhibitor which is in development for the treatment of obesity. Preclinical and clinical data suggest that appetite suppression is an important mechanism by which tesofensine exerts its robust weight reducing effect. Notably, the strong hypophagic response to tesofensine treatment is demonstrated to be linked to central stimulation of noradrenergic and dopaminergic neurotransmission. The sympathomimetic mode of action of tesofensine may also associate with the elevated heart rate and blood pressure observed in clinical settings, and we therefore sought experimentally to address this issue...
May 2013: Obesity
Giuseppe Derosa, Pamela Maffioli
INTRODUCTION: Amphetamines, rimonabant and sibutramine licenses as anti-obesity drugs have been withdrawn because of their adverse effects. In fact, orlistat is the only available long-term treatment for obesity. AREAS COVERED: The efficacy and safety of long-term drug therapy is very important in the management obesity; for this reason, the authors decided to conduct a review on the efficacy and safety of current, past and future pharmacotherapies for weight loss...
May 2012: Expert Opinion on Drug Safety
Jason C G Halford, Emma J Boyland, Clare L Lawton, John E Blundell, Joanne A Harrold
The role of serotonin (5-hydroxytryptamine) in appetite control is long established. Serotonergic manipulations reduce food intake in rodents in a manner consistent with satiety. In humans, drugs such as fenfluramine, dexfenfluramine and sibutramine all reduce energy intake, suppress hunger and enhance satiety. Effects on eating behaviour and subjective sensations of appetite are associated with the weight loss-inducing effects of these treatments. Currently, no appetite-suppressing drugs are approved specifically for the treatment of obesity...
December 3, 2011: Drugs
Pradeep J Nathan, Barry V O'Neill, Antonella Napolitano, Edward T Bullmore
INTRODUCTION: Central neurochemical systems including the monoamine, opioid, and cannabinoid systems have been promising targets for antiobesity drugs that modify behavioral components of obesity. In addition to modulating eating behavior, centrally acting antiobesity drugs are also likely to alter emotional behavior and cognitive function due to the high expression of receptors for the neurochemical systems targeted by these drugs within the fronto-striatal and limbic circuitry. METHODS: This paper reviewed the neuropsychiatric adverse effects of past and current antiobesity drugs, with a central mechanism of action, linking the adverse effects to their underlying neural substrates and neurochemistry...
October 2011: CNS Neuroscience & Therapeutics
Elsmarieke van de Giessen, Kora de Bruin, Susanne E la Fleur, Wim van den Brink, Jan Booij
The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine re-uptake and is a promising candidate for the treatment of obesity. Obesity is associated with lower striatal dopamine D2 receptor availability, which may be related to disturbed regulation of food intake. This study assesses the effects of chronic tesofensine treatment on food intake and body weight in association with changes in striatal dopamine D2/D3 receptor (D2/3R) availability of diet-induced obese (DIO) rats...
April 2012: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Jo-Anne Gilbert, Christoph Gasteyger, Anne Raben, Dieter H Meier, Arne Astrup, Anders Sjödin
Tesofensine (TE), an inhibitor of monoamine presynaptic reuptake, has produced twice the weight loss seen with currently marketed drugs. However, its long term effect on appetite in humans has not been studied. A multicentre phase II trial was divided into two parts (24 weeks each). Part 1 had a randomized, double-blind, placebo-controlled design and Part 2, an open-labeled, single-group, uncontrolled design. A drug-free period (12 ± 3 weeks) separated them. In Part 1, participants (n = 158) were assigned to 0...
March 2012: Obesity
Vojtech Hainer
Pharmacotherapy of obesity should be an integral part of the comprehensive obesity management program which includes diet, exercise and cognitive behavioural intervention. Currently available antiobesity drugs result in only modest weight loss, however it is still accompanied by reduction of cardiometabolic health risks. In the past several antiobesity drugs were removed from the market because of serious adverse effects (psychostimulatory, cardiovascular, pulmonary hypertension, valvular disease, depression, addiction etc...
2010: Casopís Lékar̆ů C̆eských
Lisa L Ioannides-Demos, Loretta Piccenna, John J McNeil
Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide)...
2011: Journal of Obesity
André M Faria, Marcio C Mancini, Maria Edna de Melo, Cintia Cercato, Alfredo Halpern
Obesity prevalence has risen dramatically over the past decades, which poses a great number of patients at risk of metabolic and cardiovascular complications. Long-term efficacy of lifestyle modification isolated has shown to be modest which, therefore, urges the need of more aggressive interventions such as adjuvant pharmacotherapy or the more radical surgical approach. Bariatric surgery has proven to date to be the most effective treatment, although it may be associated with nutritional and metabolic complications not yet completely recognized...
August 2010: Arquivos Brasileiros de Endocrinologia e Metabologia
G A Kennett, P G Clifton
In this review we assess the range of centrally active anorectics that are either in human clinical trials, or are likely to be so in the near future. We describe their weight loss efficacy, mode of action at both pharmacological and behavioural levels, where understood, together with the range of side effects that might be expected in clinical use. We have however evaluated these compounds against the considerably more rigorous criteria that are now being used by the Federal Drugs Agency and European Medicines Agency to decide approvals and market withdrawals...
November 2010: Pharmacology, Biochemistry, and Behavior
K A Schoedel, D Meier, B Chakraborty, P M Manniche, E M Sellers
Tesofensine is a (triple) reuptake inhibitor of noradrenaline, dopamine, and serotonin that is in development for the treatment of obesity. The abuse potential of triple reuptake inhibitors is not yet known, and so this study was undertaken to evaluate the potential abuse-related effects of tesofensine in humans. It was designed as a single-dose, randomized, double-blind, crossover study involving tesofensine vs. placebo, D-amphetamine (positive control for dopaminergic/stimulant effects), bupropion, and atomoxetine (negative/unscheduled controls) in recreational stimulant users (N = 52)...
July 2010: Clinical Pharmacology and Therapeutics
A Sjödin, C Gasteyger, A-Lh Nielsen, A Raben, J D Mikkelsen, J K S Jensen, D Meier, A Astrup
BACKGROUND: Tesofensine (TE) is a new drug producing twice the weight loss in obese individuals as seen with currently marketed drugs. It inhibits the presynaptic reuptake of the neurotransmitters noradrenaline, dopamine and serotonin, and is thought to enhance the neurotransmission of all three monoamines. The mechanisms by which it produces weight loss in humans are unresolved. OBJECTIVE: The aim of this study is to investigate the mechanism(s) behind weight reduction by measuring energy expenditure and appetite sensations in overweight and obese individuals...
November 2010: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Henrik H Hansen, Gitte Hansen, Mads Tang-Christensen, Philip J Larsen, Anne Marie D Axel, Anne Raben, Jens D Mikkelsen
Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of diet-induced obesity. Sibutramine and rimonabant were used as reference comparators. Compared to baseline, long-term treatment with tesofensine (28 days, 1.0 or 2.5mg/kg, p.o.) resulted in a significant, dose-dependent and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5mg/kg, p.o.) treatment caused a sustained weight loss of 7...
June 25, 2010: European Journal of Pharmacology
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