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

The sympathomimetic agent ephedrine has potent thermogenic and anti-obesity properties in rodents. The effect is markedly enhanced by caffeine, while caffeine given alone has no effect. This study was undertaken to find out if a similar weight reducing synergism between ephedrine and caffeine is present in obese patients. In a randomized, placebo-controlled, double blind study, 180 obese patients were treated by diet (4.2 MJ/day) and either an ephedrine/caffeine combination (20mg/200mg), ephedrine (20 mg), caffeine (200 mg) or placebo three times a day for 24 weeks. Withdrawals were distributed equally in the four groups, and 141 patients completed the trial. Mean weight losses was significantly greater with the combination than with placebo from week 8 to week 24 (ephedrine/caffeine, 16.6 +/- 6.8 kg vs. placebo, 13.2 +/- 6.6 kg (mean +/- s.d.), P = 0.0015). Weight loss in both the ephedrine and the caffeine groups was similar to that of the placebo group. Side effects (tremor, insomnia and dizziness) were transient and after eight weeks of treatment they had reached placebo levels. Systolic and diastolic blood pressure fell similarly in all four groups. We conclude, that in analogy with animal studies, the ephedrine/caffeine combination is effective, while caffeine and ephedrine separately are ineffective for the treatment of human obesity.
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PMID:The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. 131 81

Centrally acting appetite suppressant drugs used in the treatment of obesity fall into 2 broad pharmacological categories; those which act via brain catecholamine pathways and those which act via serotonin pathways. Of the former group, amphetamine and phenmetrazine are no longer recommended because of their stimulant properties and addictive potential. The remaining drugs in this class include amfepramone (diethylpropion), phentermine, mazindol and phenylpropanolamine. All have been shown to reduce appetite and lower food intake, thereby helping obese patients more easily keep to a low-calorie diet and lose weight. They all have some sympathomimetic and stimulant properties. Anorectic drugs which promote serotonin neurotransmission have no such stimulant or sympathomimetic properties. They are fenfluramine, together with its recently introduced dextrorotatory stereoisomer dexfenfluramine, and fluoxetine. They reduce appetite and food intake and are effective in the treatment of obesity. Anorectic drugs should be reserved for those who are clinically at risk from being overweight, and then only as part of a comprehensive weight-reducing programme including regular dietary counselling. Although current licensing regulations only allow their use over a relatively short period (12 to 16 weeks), clinical trials have shown them to be effective over longer periods, particularly in preventing weight regain. Of the compounds currently indicated for use in obesity, dexfenfluramine appears to have the most suitable pharmacological profile, although it should not be given to patients with a history of depression. When used appropriately, appetite suppressants can be of real therapeutic benefit, and pose little risk.
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PMID:Appetite suppressants. A review. 137 55

Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate.
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PMID:Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? 143 97

The authors summarize the principles of the therapeutic approach to the 5H syndrome [1. hyperinsulinism, 2. hyperglycaemia (NIDDM), 3. hyperlipoproteinaemia (obesity), 4. hypertension, 5. hirsutism], in particular its two components, i.e. NIDDM and arterial hypertension. The authors found that early treatment of hyperinsulinism, e.g. already in the stage of impaired glucose tolerance or NIDDM with oral antidiabetics, their disproportionate increase with regard to the blood sugar level and glycosylated haemoglobin without making "hygienic" provisions (radical weight reduction; increased physical activity to the maximum possible individual level; energy restricted diet in particular as regards carbohydrates and fat) does not prevent progression of the components of the 5H syndrome to the clinical stage. In treatment of arterial hypertension associated with 5H syndrome non-selective beta-blockers and thiazide diuretics are unsuitable because they worsen the HPLP and enhance insulin resistance. Suitable preparations are combinations of ACE-inhibitors, calcium antagonists, selective beta-blockers in particular with ISA and beta-blockers with a partial selective sympathomimetic activity (devalol and celiprolol). Hygienic provisions must be started in childhood, or when hyperinsulinism is detected.
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PMID:[How should we implement the basic principles of treatment of type 2 diabetes mellitus from the aspect of the hormono-metabolic syndrome X (5H)?]. 145 53

Adipsin gene expression is severely diminished in certain forms of genetic and acquired rodent obesity. Common to many of these models of obesity is decreased sympathetic nervous system (SNS) activity. In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity. Based on these observations, we hypothesized that adipsin gene expression might be regulated through changes in SNS activity with deficient adipsin gene expression in obesity being the result of impaired SNS activity. In the present study we used three models to assess the role of the SNS in regulating adipsin gene expression. First we exposed mice to the cold (4 degrees C), a potent activator of SNS activity. Second, we chemically sympathectomized mice with 60H-dopamine. Third, we treated mice with BRL 26830A, an atypical beta adrenoreceptor agonist. In contrast to our initial hypothesis, these studies demonstrate that alterations of SNS activity do not affect adipsin gene expression in normal mice. Neither increased SNS activity secondary to cold exposure nor decreased SNS activity resulting from sympathectomy alter serum adipsin concentration or adipsin mRNA levels in white (WAT) and brown adipose tissue (BAT). Surprisingly, treatment of lean mice with BRL 26830A decreases both adipsin serum concentrations and adipsin mRNA levels, suggesting a potential role for atypical beta adrenoreceptors in pathways that suppress adipsin expression in vivo. The significance of this observation with respect to adipocyte physiology is unclear at present. Future studies will be aimed at defining the molecular mechanisms by which BRL 26830A suppresses adipsin gene expression and the physiological significance of this effect.
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PMID:Alterations in sympathetic nervous system activity do not regulate adipsin gene expression in mice. 164 81

The position of pharmacotherapy of obesity is still controversial. Different groups of drugs are currently available in Switzerland--none is covered by the health insurances. Apparently the authorities are not convinced of their efficacy. Various groups of drugs have been tried, such as amphetamine derivatives, adrenergic drugs, serotonin agonists or hormones with thermogenic effects, intestinal enzyme inhibitors and dietary fibres. The results of sympathomimetic drugs demonstrate a relatively high incidence of side-effects, and with some preparations there is also the risk of addiction. The serotoninergic drug fenfluramine has been demonstrated in several controlled studies to be an effective weight-reducing agent; however, its effect was relatively modest: It lasted only as long as the drug was taken. Fenfluramine is relatively free of side-effects and is reported to diminish 'carbohydrate craving'.
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PMID:[Drugs against obesity]. 217 Nov 53

Dexfenfluramine, the dextrostereoisomer of fenfluramine, is a pure serotonin (5-hydroxytryptamine) agonist, apparently devoid of any additional antidopaminergic or sympathomimetic effects. The drug is approximately twice as effective as its racemic predecessor in reducing food intake in animals, and at a dose of 30 mg/day dexfenfluramine substantially modifies eating behaviour in man. Thus, a reduction in the motivation to eat and fewer snacking episodes were seen in volunteers treated with the drug, while total caloric and carbohydrate (but not protein) intakes were reduced in obese carbohydrate cravers. In clinical studies in obesity, dexfenfluramine combined with dietary support has produced mean weight reductions superior to those achieved with placebo over 3-month treatment periods. Importantly, the drug appears to maintain its weight-reducing effects for at least 12 months, without serious adverse effects. Dexfenfluramine appears to possess many of the properties of an 'ideal' pharmacotherapeutic agent for obesity. However, further long term clinical studies are required to confirm the promising efficacy and safety data obtained to date, and to further define the most appropriate indications for its use. Ideally, the drug should be used as adjunctive treatment in the clinical management of more severe cases of obesity, which are refractory to simpler supportive measures such as dietary or psychological counseling.
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PMID:Dexfenfluramine. Its place in weight control. 219 76

Adipsin gene expression is greatly diminished in certain forms of genetic and acquired obesity. In the present study we evaluate the time course for the development of adipsin deficiency in obesity and its regulation by the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Previously, it was unknown whether adipsin deficiency occurred before or after the development of massive obesity. In the first series of experiments in which mice were treated with monosodium glutamate (MSG) for the first week of life, we demonstrate that adipsin deficiency occurs early in the development of MSG-induced obesity as evidenced by decreased circulating adipsin concentrations by 1 week of age and deficient adipsin mRNA levels in white adipose tissue (WAT) by 2 weeks. In db/db mice, diminished circulating adipsin was noted at 2 weeks of age. In both models, decreased adipsin gene expression precedes the development of marked obesity. Little is known about the factors which regulate adipsin gene expression in obesity. Common to the ob/ob, db/db and MSG models is diminished thermogenesis and sympathetic nervous system activity. In a second series of experiments we sought to determine whether adipsin deficiency in obesity could be corrected by treatment with ephedrine and caffeine (E+C), a sympathomimetic-thermogenic mixture previously shown to increase thermogenesis and reverse obesity in some models. In the present study, E+C treatment of MSG obese mice reversed obesity and markedly increased serum adipsin and adipsin mRNA levels in WAT and brown adipose tissue (BAT). In ob/ob mice, however, E+C treatment produced a negligible increase in adipsin mRNA levels in WAT and BAT as well as serum adipsin concentrations and this correlated with only a very small decrease in obesity. Thus, the ability of E+C to increase adipsin gene expression correlated with its ability to reverse obesity in these two models. Finally, the effect of E+C on adipsin gene expression may not be exerted directly on the fat cell since treatment of cultured 3T3-F442A adipocytes and isolated rat adipocytes in primary culture produced no effect on adipsin mRNA or secreted protein despite a lipolytic effect as measured by increased glycerol release. In summary, decreased adipsin gene expression occurs early in the development of MSG and db/db obesity and is markedly increased in the MSG model by the sympathomimetic-thermogenic drug mixture, E+C, which also reverses obesity. Elucidation of the factors responsible for these effects may enhance our understanding of fat cell gene regulation and obesity.
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PMID:Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. 230 16

The effect of CGP-12177, originally developed as a radioligand with antagonist properties for binding studies of beta-adrenergic receptors, was investigated in brown adipose tissue. Contrary to expectations, CGP-12177 showed clear agonist properties in experiments with hamster brown-fat cells, with a maximal effect in stimulating oxygen consumption similar to that of the physiological stimulator noradrenaline, and also with a potency similar to that of noradrenaline [EC50 (50% effective concn.) approx. 70 nM]. This value could be contrasted with the very high affinity of CGP-12177 (KD about 1 nM) for ligand-binding sites on the cells. It is therefore suggested that the high-affinity binding site may not be the one that mediates the CGP-12177-stimulated thermogenesis in isolated cells. Also, when injected into cold-adapted rats, CGP-12177 stimulated non-shivering thermogenesis similarly to noradrenaline. This observation, in conjunction with the reported low general sympathomimetic effect of CGP-12177, may indicate that CGP-12177 could be of interest for the development of anti-obesity drugs.
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PMID:The beta-adrenergic radioligand [3H]CGP-12177, generally classified as an antagonist, is a thermogenic agonist in brown adipose tissue. 257 May 69

In general, rises in systolic blood pressure to over 200 mm Hg during exercise with a workload of 100W are regarded as pathological. Excessive exercise blood pressure values are to be expected in principle in all hypertensives. However, there are so far no generally accepted criteria for diagnosis of isolated systolic exercise hypertension (with normal values of resting blood pressure). The incidence of isolated systolic exercise hypertension is estimated to be about 10% of a selected population. In patients with excessive rises in blood pressure during exercise who want to engage actively in sport, general measures (reduction of obesity, restriction of alcohol and salt intake) and endurance training should be recommended initially. For endurance training, sporting activities that involve dynamic exercise are to be recommended (walking, running, mountain hiking, cycling, swimming, cross-country skiing). Activities involving isometric exercise (rowing, diving, tennis) and sport of a competitive nature are not suitable. In moderately severe and severe hypertension (diastolic blood pressure values in excess of 105 mm Hg), sporting activities and endurance training are contraindicated. If the exercise blood pressure values cannot be lowered below 220 mm Hg with the general measures mentioned, pharmacotherapy is to be considered. The drugs of choice for suppressing excessive rises in blood pressure during exercise are beta-blockers. In this group, beta 1-blockers are to be preferred to non-selective beta-blockers because of the metabolic neutrality of the former. beta-Blockers without intrinsic sympathomimetic activity (ISA) lower the blood pressure-pulse rate product more effectively than beta-blockers with ISA. Alternatively, calcium antagonists of the verapamil type and ACE inhibitors can be employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of hypertension in actively exercising patients. Implications for drug selection. 264 57


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