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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drugs are part of the multimodal approach of modern obesity treatment. In the near future Sibutramine, a centrally acting serotoninergic and noradrenergic agonist and Orlistat, a peripherally acting lipase inhibitor will be available for treatment of obesity. Since all drugs employed should be applicable for years the latter substance might be especially useful for the mandatory longterm treatment of obese patients.
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PMID:[What is the role of drugs in therapy of obesity?]. 988 2

1. The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. 2. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg(-1) of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5-1.0 degrees C) in body temperature. 3. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). 4. Combined high, non-selective doses (20 mg kg(-1)) of the beta-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, beta1-adrenoceptor-selective (atenolol) or beta2-adrenoceptor-selective (ICI 118551) doses (1 mg kg(-1)). 5. The ganglionic blocking agent, chlorisondamine (15 mg kg(-1)), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the beta3-adrenoceptor-selective agonist BRL 35135. 6. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg(-1)) that had no effect on VO2 when injected individually. 7. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via beta3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent.
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PMID:Thermogenic effects of sibutramine and its metabolites. 1021 44

Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction should be considered as a key objective. In this respect, several antiobesity drugs have demonstrated potential. However, while fenfluramine and dexfenfluramine have been shown to promote weight loss and to directly improve insulin sensitivity, being two mechanisms contributing to better blood glucose control in obese Type 2 diabetic patients, they were recently withdrawn due to safety problems. Sibutramine, a new selective norepinephrine and serotonin reuptake inhibitor, promotes weight loss by decreasing food intake, an effect which leads to a mild improvement (significant in patients losing > or =5% of initial body weight) of blood glucose control in obese diabetic patients. Similarly, orlistat, a selective gastrointestinal lipase inhibitor which increases faecal fat losses, enhances diet-induced weight reduction and improves both blood glucose control and vascular risk profile, especially dyslipidaemia, in obese Type 2 diabetic patients. Further studies are required to better identify good responders to pharmacotherapy and specify the role of antiobesity agents in the overall long-term management of obese subjects with Type 2 diabetes. Other novel pharmacological approaches deserve further consideration, for instance beta-3 agonists aiming to increase energy expenditure, drugs interfering with tumor necrosis factor-alpha (TNF-alpha) or free fatty acid release by the adipose tissue or agents that slow gastric emptying. However, until now, results regarding efficacy and/or safety have been disappointing or preliminary in humans.
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PMID:Antiobesity pharmacotherapy in the management of type 2 diabetes. 1075 51

Obesity is one of the most common medical problems in the United States and a risk factor for illnesses such as hypertension, diabetes, degenerative arthritis and myocardial infarction. It is a cause of significant morbidity and mortality and generates great social and financial costs. Obesity is defined as a body mass index greater than 30. Many patients accomplish weight loss with diet, exercise and lifestyle modification. Others require more aggressive therapy. Weight loss medications may be appropriate for use in selected patients who meet the definition of obesity or who are overweight with comorbid conditions. Medications are formulated to reduce energy intake, increase energy output or decrease the absorption of nutrients. Drugs cannot replace diet, exercise and lifestyle modification, which remain the cornerstones of obesity treatment. Two new agents, sibutramine and orlistat, exhibit novel mechanisms of action and avoid some of the side effects that occurred with earlier drugs. Sibutramine acts to block uptake of serotonin, norepinephrine and dopamine, while orlistat decreases fat absorption in the intestines.
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PMID:Medical management of obesity. 1092 4

Drugs to treat obesity can be divided into three groups: those which reduce food intake, those which alter metabolism and those which increase thermogenesis. Monoamines acting on noradrenergic receptors, serotonin receptors, dopamine receptors and histamine receptors can reduce food intake. A number of peptides also affect food intake. The noradrenergic drugs phentermine, diethylpropion, mazindol benzphetamine and phendimetrazine are approved only for short-term use. Sibutramine, a norepinephrine-serotonin re-uptake inhibitor, is approved for long-term use. Orlistat inhibits pancreatic lipase and can block 30% of triglyceride hydrolysis in subjects eating a 30% fat diet. The only thermogenic drug combination that has been tested is ephedrine and caffeine, but this treatment has not been approved by regulating agencies. Leptin is currently in clinical trials and other drugs that may modulate peptide-feeding systems are being developed.
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PMID:Drug treatment of obesity. 1093 81

Drugs to treat obesity can be divided into three groups: those that reduce food intake; those that alter metabolism; and those that increase thermogenesis. Monoamines acting on noradrenergic receptors, serotonin receptors, dopamine receptors, and histamine receptors can reduce food intake. A number of peptides also affect food intake. The noradrenergic drugs phentermine, diethylpropion, mazindol, benzphetamine, and phendimetrazine are approved only for short-term use. Sibutramine, a norepinephrine-serotonin reuptake inhibitor, is approved for long-term use. Orlistat inhibits pancreatic lipase and can block 30% of the triacylglycerol hydrolysis in subjects eating a 30% fat diet. The only thermogenic drug combination that has been tested is ephedrine and caffeine, but this treatment has not been approved by regulatory agencies. In clinical trials other drugs that may modulate peptide-feeding systems are being developed.
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PMID:A concise review on the therapeutics of obesity. 1105 1

Physicians have struggled with the pharmacological treatment of obesity. In the past, thyroid hormone was often used inappropriately. Dangerous drugs such as dinitrophenol and amphetamines were prescribed, with serious side effects. In the 1980s, a 3 1/2-year study using antiobesity medications with different mechanisms of action supported the theory that patients treated with combination therapy experienced greater weight loss than the placebo-treated patients and that those who remained on therapy were more likely to keep the weight off. Thus, physicians began prescribing "fen-phen" to their patients in the mid-1990s. In 1997, manufacturers voluntarily withdraw the fenfluramines from the market after study results linked their use with valvular heart disease. Since then, two new drugs with different mechanisms of action have been approved for use by the FDA. Sibutramine (Meridia) is a serotonin-norepinephrine reuptake inhibitor acting on the appetite center in the hypothalamus, and orlistat (Xenical) is a pancreatic lipase inhibitor. Research on antiobesity drugs continues. More than 30 potentially new drugs are in various stages of research. It could be years, however, before any of them are proven useful and safe. Antiobesity pharmacology is meant to be used as a tool to treat the disease. Lifestyle changes in the form of diet and exercise patterns are still the crux of therapy.
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PMID:Pharmacological treatment of obesity. Past, present, and future. 1112 76

An overweight patient (body mass index of 34 kg/m(2)) with narcolepsy associated with cataplexy is described. Polysomnography did not indicate obstructive sleep apnea. Her obesity was treated with sibutramine, a norepinephrine, serotonin and dopamine reuptake inhibiting medication and her severe cataplexy remitted. Clinicians must be aware that sibutramine may suppress cataplexy when evaluating excessive daytime sleepiness in an overweight patient taking this anti-obesity medication. Therefore a negative history of cataplexy in these cases may be misleading and narcolepsy may be overlooked in the differential diagnosis. Sibutramine should be discontinued before polysomnography and multiple sleep latency testing but may be a useful medication in the management of obese narcoleptic patients with cataplexy. With the discovery of decreased hypocretin 1 levels in humans with narcolepsy, a neuropeptide that modulates sleep and feeding, the association between narcolepsy and obesity requires more attention.
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PMID:Narcolepsy and obesity: remission of severe cataplexy with sibutramine. 1115 84

We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones. Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg(-1) day(-1) p.o.) or deionized water for 21 days. Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean (P<0.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were significantly more insulin resistant than controls (P<0.005), and this was corrected by sibutramine treatment (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were significantly altered by sibutramine compared to untreated controls. The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones.
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PMID:Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y. 1130 62

The socio-economic impact of obesity, one of the most prevalent medical disorders in Western society, is mainly due to its association with a higher risk of coronary heart disease. It is likely that atherosclerosis develops against a background of obesity as a result of the insulin resistance that is invariably present in overweight and obese subjects. Fasting plasma lipids may be normal in obese subjects, but they are usually affected by postprandial hyperlipidemia, which is probably due to competition between chylomicrons and VLDL for the same metabolic pathways. The basis for the impaired clearance of atherogenic chylomicron remnants is the fact that obesity causes hepatic apo B-VLDL overproduction, and thus leads to competition with chylomicrons and their remnants at the lipolytic pathway (lipoprotein lipase and hepatic lipase) and receptor level (LDL-receptor and remnant-receptor). The overproduction of VLDL is probably caused by an enhanced hepatic flux of free fatty acids in both the postprandial (from the lipolysis of triglyceride rich particles) and postabsorptive states (from adipocytes). Weight reduction by means of life-style changes, supported by medical interventions with inhibitors of intestinal fat absorption (e.g. Orlistat) or appetite suppressants (e.g. Sibutramine), is essential in order to decrease the risk of atherosclerosis. Furthermore, improvement of risk factors can be achieved by means of fibrate treatment to modulate fasting and postprandial triglyceride levels. Treatment with cholesterol synthesis inhibitors ("statins") may reduce hepatic VLDL production and increase the clearance of atherogenic remnants by upregulating LDL-receptors, thus leading to improved fasting lipid levels and enhanced clearance of chylomicron remnants. Finally, the use of thiazolidinedione derivatives to improve insulin sensitivity may be one of the options for reducing the risk of atherosclerosis in obese subjects.
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PMID:Obesity and free fatty acids: double trouble. 1143 90


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